---
_id: '10791'
abstract:
- lang: eng
text: The mammalian neocortex is composed of diverse neuronal and glial cell classes
that broadly arrange in six distinct laminae. Cortical layers emerge during development
and defects in the developmental programs that orchestrate cortical lamination
are associated with neurodevelopmental diseases. The developmental principle of
cortical layer formation depends on concerted radial projection neuron migration,
from their birthplace to their final target position. Radial migration occurs
in defined sequential steps, regulated by a large array of signaling pathways.
However, based on genetic loss-of-function experiments, most studies have thus
far focused on the role of cell-autonomous gene function. Yet, cortical neuron
migration in situ is a complex process and migrating neurons traverse along diverse
cellular compartments and environments. The role of tissue-wide properties and
genetic state in radial neuron migration is however not clear. Here we utilized
mosaic analysis with double markers (MADM) technology to either sparsely or globally
delete gene function, followed by quantitative single-cell phenotyping. The MADM-based
gene ablation paradigms in combination with computational modeling demonstrated
that global tissue-wide effects predominate cell-autonomous gene function albeit
in a gene-specific manner. Our results thus suggest that the genetic landscape
in a tissue critically affects the overall migration phenotype of individual cortical
projection neurons. In a broader context, our findings imply that global tissue-wide
effects represent an essential component of the underlying etiology associated
with focal malformations of cortical development in particular, and neurological
diseases in general.
acknowledged_ssus:
- _id: LifeSc
- _id: PreCl
- _id: Bio
acknowledgement: "A.H.H. was a recipient of a DOC Fellowship (24812) of the Austrian
Academy of Sciences. This work also received support from IST Austria institutional
funds; the People Programme (Marie Curie Actions) of the European Union’s Seventh
Framework Programme (FP7/2007–2013) under REA grant agreement No 618444 to S.H.\r\nAPC
funding was obtained by IST Austria institutional funds.\r\nWe thank A. Sommer and
C. Czepe (VBCF GmbH, NGS Unit), L. Andersen, J. Sonntag and J. Renno for technical
support and/or initial experiments; M. Sixt, J. Nimpf and all members of the Hippenmeyer
lab for discussion. This research was supported by the Scientific Service Units
of IST Austria through resources provided by the Imaging and Optics Facility, Lab
Support Facility and Preclinical Facility."
article_number: kvac009
article_processing_charge: No
article_type: original
author:
- first_name: Andi H
full_name: Hansen, Andi H
id: 38853E16-F248-11E8-B48F-1D18A9856A87
last_name: Hansen
- first_name: Florian
full_name: Pauler, Florian
id: 48EA0138-F248-11E8-B48F-1D18A9856A87
last_name: Pauler
orcid: 0000-0002-7462-0048
- first_name: Michael
full_name: Riedl, Michael
id: 3BE60946-F248-11E8-B48F-1D18A9856A87
last_name: Riedl
orcid: 0000-0003-4844-6311
- first_name: Carmen
full_name: Streicher, Carmen
id: 36BCB99C-F248-11E8-B48F-1D18A9856A87
last_name: Streicher
- first_name: Anna-Magdalena
full_name: Heger, Anna-Magdalena
id: 4B76FFD2-F248-11E8-B48F-1D18A9856A87
last_name: Heger
- first_name: Susanne
full_name: Laukoter, Susanne
id: 2D6B7A9A-F248-11E8-B48F-1D18A9856A87
last_name: Laukoter
orcid: 0000-0002-7903-3010
- first_name: Christoph M
full_name: Sommer, Christoph M
id: 4DF26D8C-F248-11E8-B48F-1D18A9856A87
last_name: Sommer
orcid: 0000-0003-1216-9105
- first_name: Armel
full_name: Nicolas, Armel
id: 2A103192-F248-11E8-B48F-1D18A9856A87
last_name: Nicolas
- first_name: Björn
full_name: Hof, Björn
id: 3A374330-F248-11E8-B48F-1D18A9856A87
last_name: Hof
orcid: 0000-0003-2057-2754
- first_name: Li Huei
full_name: Tsai, Li Huei
last_name: Tsai
- first_name: Thomas
full_name: Rülicke, Thomas
last_name: Rülicke
- first_name: Simon
full_name: Hippenmeyer, Simon
id: 37B36620-F248-11E8-B48F-1D18A9856A87
last_name: Hippenmeyer
orcid: 0000-0003-2279-1061
citation:
ama: Hansen AH, Pauler F, Riedl M, et al. Tissue-wide effects override cell-intrinsic
gene function in radial neuron migration. Oxford Open Neuroscience. 2022;1(1).
doi:10.1093/oons/kvac009
apa: Hansen, A. H., Pauler, F., Riedl, M., Streicher, C., Heger, A.-M., Laukoter,
S., … Hippenmeyer, S. (2022). Tissue-wide effects override cell-intrinsic gene
function in radial neuron migration. Oxford Open Neuroscience. Oxford Academic.
https://doi.org/10.1093/oons/kvac009
chicago: Hansen, Andi H, Florian Pauler, Michael Riedl, Carmen Streicher, Anna-Magdalena
Heger, Susanne Laukoter, Christoph M Sommer, et al. “Tissue-Wide Effects Override
Cell-Intrinsic Gene Function in Radial Neuron Migration.” Oxford Open Neuroscience.
Oxford Academic, 2022. https://doi.org/10.1093/oons/kvac009.
ieee: A. H. Hansen et al., “Tissue-wide effects override cell-intrinsic gene
function in radial neuron migration,” Oxford Open Neuroscience, vol. 1,
no. 1. Oxford Academic, 2022.
ista: Hansen AH, Pauler F, Riedl M, Streicher C, Heger A-M, Laukoter S, Sommer CM,
Nicolas A, Hof B, Tsai LH, Rülicke T, Hippenmeyer S. 2022. Tissue-wide effects
override cell-intrinsic gene function in radial neuron migration. Oxford Open
Neuroscience. 1(1), kvac009.
mla: Hansen, Andi H., et al. “Tissue-Wide Effects Override Cell-Intrinsic Gene Function
in Radial Neuron Migration.” Oxford Open Neuroscience, vol. 1, no. 1, kvac009,
Oxford Academic, 2022, doi:10.1093/oons/kvac009.
short: A.H. Hansen, F. Pauler, M. Riedl, C. Streicher, A.-M. Heger, S. Laukoter,
C.M. Sommer, A. Nicolas, B. Hof, L.H. Tsai, T. Rülicke, S. Hippenmeyer, Oxford
Open Neuroscience 1 (2022).
date_created: 2022-02-25T07:52:11Z
date_published: 2022-07-07T00:00:00Z
date_updated: 2023-11-30T10:55:12Z
day: '07'
ddc:
- '570'
department:
- _id: SiHi
- _id: BjHo
- _id: LifeSc
- _id: EM-Fac
doi: 10.1093/oons/kvac009
ec_funded: 1
file:
- access_level: open_access
checksum: 822e76e056c07099d1fb27d1ece5941b
content_type: application/pdf
creator: dernst
date_created: 2023-08-16T08:00:30Z
date_updated: 2023-08-16T08:00:30Z
file_id: '14061'
file_name: 2023_OxfordOpenNeuroscience_Hansen.pdf
file_size: 4846551
relation: main_file
success: 1
file_date_updated: 2023-08-16T08:00:30Z
has_accepted_license: '1'
intvolume: ' 1'
issue: '1'
language:
- iso: eng
license: https://creativecommons.org/licenses/by/4.0/
month: '07'
oa: 1
oa_version: Published Version
project:
- _id: 25D61E48-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '618444'
name: Molecular Mechanisms of Cerebral Cortex Development
- _id: 2625A13E-B435-11E9-9278-68D0E5697425
grant_number: '24812'
name: Molecular Mechanisms of Radial Neuronal Migration
publication: Oxford Open Neuroscience
publication_identifier:
eissn:
- 2753-149X
publication_status: published
publisher: Oxford Academic
quality_controlled: '1'
related_material:
record:
- id: '12726'
relation: dissertation_contains
status: public
- id: '14530'
relation: dissertation_contains
status: public
status: public
title: Tissue-wide effects override cell-intrinsic gene function in radial neuron
migration
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 1
year: '2022'
...
---
_id: '9429'
abstract:
- lang: eng
text: De novo loss of function mutations in the ubiquitin ligase-encoding gene Cullin3
lead to autism spectrum disorder (ASD). In mouse, constitutive haploinsufficiency
leads to motor coordination deficits as well as ASD-relevant social and cognitive
impairments. However, induction of Cul3 haploinsufficiency later in life does
not lead to ASD-relevant behaviors, pointing to an important role of Cul3 during
a critical developmental window. Here we show that Cul3 is essential to regulate
neuronal migration and, therefore, constitutive Cul3 heterozygous mutant mice
display cortical lamination abnormalities. At the molecular level, we found that
Cul3 controls neuronal migration by tightly regulating the amount of Plastin3
(Pls3), a previously unrecognized player of neural migration. Furthermore, we
found that Pls3 cell-autonomously regulates cell migration by regulating actin
cytoskeleton organization, and its levels are inversely proportional to neural
migration speed. Finally, we provide evidence that cellular phenotypes associated
with autism-linked gene haploinsufficiency can be rescued by transcriptional activation
of the intact allele in vitro, offering a proof of concept for a potential therapeutic
approach for ASDs.
acknowledged_ssus:
- _id: PreCl
acknowledgement: We thank A. Coll Manzano, F. Freeman, M. Ladron de Guevara, and A.
Ç. Yahya for technical assistance, S. Deixler, A. Lepold, and A. Schlerka for the
management of our animal colony, as well as M. Schunn and the Preclinical Facility
team for technical assistance. We thank K. Heesom and her team at the University
of Bristol Proteomics Facility for the proteomics sample preparation, data generation,
and analysis support. We thank Y. B. Simon for kindly providing the plasmid for
lentiviral labeling. Further, we thank M. Sixt for his advice regarding cell migration
and the fruitful discussions. This work was supported by the ISTPlus postdoctoral
fellowship (Grant Agreement No. 754411) to B.B., by the European Union’s Horizon
2020 research and innovation program (ERC) grant 715508 (REVERSEAUTISM), and by
the Austrian Science Fund (FWF) to G.N. (DK W1232-B24 and SFB F7807-B) and to J.G.D
(I3600-B27).
article_number: '3058'
article_processing_charge: No
article_type: original
author:
- first_name: Jasmin
full_name: Morandell, Jasmin
id: 4739D480-F248-11E8-B48F-1D18A9856A87
last_name: Morandell
- first_name: Lena A
full_name: Schwarz, Lena A
id: 29A8453C-F248-11E8-B48F-1D18A9856A87
last_name: Schwarz
- first_name: Bernadette
full_name: Basilico, Bernadette
id: 36035796-5ACA-11E9-A75E-7AF2E5697425
last_name: Basilico
orcid: 0000-0003-1843-3173
- first_name: Saren
full_name: Tasciyan, Saren
id: 4323B49C-F248-11E8-B48F-1D18A9856A87
last_name: Tasciyan
orcid: 0000-0003-1671-393X
- first_name: Georgi A
full_name: Dimchev, Georgi A
id: 38C393BE-F248-11E8-B48F-1D18A9856A87
last_name: Dimchev
orcid: 0000-0001-8370-6161
- first_name: Armel
full_name: Nicolas, Armel
id: 2A103192-F248-11E8-B48F-1D18A9856A87
last_name: Nicolas
- first_name: Christoph M
full_name: Sommer, Christoph M
id: 4DF26D8C-F248-11E8-B48F-1D18A9856A87
last_name: Sommer
orcid: 0000-0003-1216-9105
- first_name: Caroline
full_name: Kreuzinger, Caroline
id: 382077BA-F248-11E8-B48F-1D18A9856A87
last_name: Kreuzinger
- first_name: Christoph
full_name: Dotter, Christoph
id: 4C66542E-F248-11E8-B48F-1D18A9856A87
last_name: Dotter
orcid: 0000-0002-9033-9096
- first_name: Lisa
full_name: Knaus, Lisa
id: 3B2ABCF4-F248-11E8-B48F-1D18A9856A87
last_name: Knaus
- first_name: Zoe
full_name: Dobler, Zoe
id: D23090A2-9057-11EA-883A-A8396FC7A38F
last_name: Dobler
- first_name: Emanuele
full_name: Cacci, Emanuele
last_name: Cacci
- first_name: Florian KM
full_name: Schur, Florian KM
id: 48AD8942-F248-11E8-B48F-1D18A9856A87
last_name: Schur
orcid: 0000-0003-4790-8078
- first_name: Johann G
full_name: Danzl, Johann G
id: 42EFD3B6-F248-11E8-B48F-1D18A9856A87
last_name: Danzl
orcid: 0000-0001-8559-3973
- first_name: Gaia
full_name: Novarino, Gaia
id: 3E57A680-F248-11E8-B48F-1D18A9856A87
last_name: Novarino
orcid: 0000-0002-7673-7178
citation:
ama: Morandell J, Schwarz LA, Basilico B, et al. Cul3 regulates cytoskeleton protein
homeostasis and cell migration during a critical window of brain development.
Nature Communications. 2021;12(1). doi:10.1038/s41467-021-23123-x
apa: Morandell, J., Schwarz, L. A., Basilico, B., Tasciyan, S., Dimchev, G. A.,
Nicolas, A., … Novarino, G. (2021). Cul3 regulates cytoskeleton protein homeostasis
and cell migration during a critical window of brain development. Nature Communications.
Springer Nature. https://doi.org/10.1038/s41467-021-23123-x
chicago: Morandell, Jasmin, Lena A Schwarz, Bernadette Basilico, Saren Tasciyan,
Georgi A Dimchev, Armel Nicolas, Christoph M Sommer, et al. “Cul3 Regulates Cytoskeleton
Protein Homeostasis and Cell Migration during a Critical Window of Brain Development.”
Nature Communications. Springer Nature, 2021. https://doi.org/10.1038/s41467-021-23123-x.
ieee: J. Morandell et al., “Cul3 regulates cytoskeleton protein homeostasis
and cell migration during a critical window of brain development,” Nature Communications,
vol. 12, no. 1. Springer Nature, 2021.
ista: Morandell J, Schwarz LA, Basilico B, Tasciyan S, Dimchev GA, Nicolas A, Sommer
CM, Kreuzinger C, Dotter C, Knaus L, Dobler Z, Cacci E, Schur FK, Danzl JG, Novarino
G. 2021. Cul3 regulates cytoskeleton protein homeostasis and cell migration during
a critical window of brain development. Nature Communications. 12(1), 3058.
mla: Morandell, Jasmin, et al. “Cul3 Regulates Cytoskeleton Protein Homeostasis
and Cell Migration during a Critical Window of Brain Development.” Nature Communications,
vol. 12, no. 1, 3058, Springer Nature, 2021, doi:10.1038/s41467-021-23123-x.
short: J. Morandell, L.A. Schwarz, B. Basilico, S. Tasciyan, G.A. Dimchev, A. Nicolas,
C.M. Sommer, C. Kreuzinger, C. Dotter, L. Knaus, Z. Dobler, E. Cacci, F.K. Schur,
J.G. Danzl, G. Novarino, Nature Communications 12 (2021).
date_created: 2021-05-28T11:49:46Z
date_published: 2021-05-24T00:00:00Z
date_updated: 2024-09-10T12:04:26Z
day: '24'
ddc:
- '572'
department:
- _id: GaNo
- _id: JoDa
- _id: FlSc
- _id: MiSi
- _id: LifeSc
- _id: Bio
doi: 10.1038/s41467-021-23123-x
ec_funded: 1
external_id:
isi:
- '000658769900010'
file:
- access_level: open_access
checksum: 337e0f7959c35ec959984cacdcb472ba
content_type: application/pdf
creator: kschuh
date_created: 2021-05-28T12:39:43Z
date_updated: 2021-05-28T12:39:43Z
file_id: '9430'
file_name: 2021_NatureCommunications_Morandell.pdf
file_size: 9358599
relation: main_file
success: 1
file_date_updated: 2021-05-28T12:39:43Z
has_accepted_license: '1'
intvolume: ' 12'
isi: 1
issue: '1'
keyword:
- General Biochemistry
- Genetics and Molecular Biology
language:
- iso: eng
month: '05'
oa: 1
oa_version: Published Version
project:
- _id: 260C2330-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '754411'
name: ISTplus - Postdoctoral Fellowships
- _id: 25444568-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '715508'
name: Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo
and in vitro Models
- _id: 2548AE96-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: W1232-B24
name: Molecular Drug Targets
- _id: 05A0D778-7A3F-11EA-A408-12923DDC885E
grant_number: F07807
name: Neural stem cells in autism and epilepsy
- _id: 265CB4D0-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: I03600
name: Optical control of synaptic function via adhesion molecules
publication: Nature Communications
publication_identifier:
eissn:
- 2041-1723
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
related_material:
link:
- relation: press_release
url: https://ist.ac.at/en/news/defective-gene-slows-down-brain-cells/
record:
- id: '7800'
relation: earlier_version
status: public
- id: '12401'
relation: dissertation_contains
status: public
status: public
title: Cul3 regulates cytoskeleton protein homeostasis and cell migration during a
critical window of brain development
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 12
year: '2021'
...
---
_id: '10117'
abstract:
- lang: eng
text: Proximity labeling provides a powerful in vivo tool to characterize the proteome
of subcellular structures and the interactome of specific proteins. The nematode
Caenorhabditis elegans is one of the most intensely studied organisms in biology,
offering many advantages for biochemistry. Using the highly active biotin ligase
TurboID, we optimize here a proximity labeling protocol for C. elegans. An advantage
of TurboID is that biotin's high affinity for streptavidin means biotin-labeled
proteins can be affinity-purified under harsh denaturing conditions. By combining
extensive sonication with aggressive denaturation using SDS and urea, we achieved
near-complete solubilization of worm proteins. We then used this protocol to characterize
the proteomes of the worm gut, muscle, skin, and nervous system. Neurons are among
the smallest C. elegans cells. To probe the method's sensitivity, we expressed
TurboID exclusively in the two AFD neurons and showed that the protocol could
identify known and previously unknown proteins expressed selectively in AFD. The
active zones of synapses are composed of a protein matrix that is difficult to
solubilize and purify. To test if our protocol could solubilize active zone proteins,
we knocked TurboID into the endogenous elks-1 gene, which encodes a presynaptic
active zone protein. We identified many known ELKS-1-interacting active zone proteins,
as well as previously uncharacterized synaptic proteins. Versatile vectors and
the inherent advantages of using C. elegans, including fast growth and the ability
to rapidly make and functionally test knock-ins, make proximity labeling a valuable
addition to the armory of this model organism.
acknowledgement: We thank de Bono lab members for helpful comments on the manuscript,
IST Austria and University of Vienna Mass Spec Facilities for invaluable discussions
and comments for the optimization of mass spec analyses of worm samples. The biotin
auxotropic E. coli strain MG1655bioB:kan was gift from John Cronan (University of
Illinois) and was kindly sent to us by Jessica Feldman and Ariana Sanchez (Stanford
University). dg398 pEntryslot2_mNeongreen::3XFLAG::stop and dg397 pEntryslot3_mNeongreen::3XFLAG::stop::unc-54
3′UTR entry vector were kindly shared by Dr Dominique Glauser (University of Fribourg).
Codon-optimized mScarlet vector was a generous gift from Dr Manuel Zimmer (University
of Vienna).
article_number: '101094'
article_processing_charge: Yes
article_type: original
author:
- first_name: Murat
full_name: Artan, Murat
id: C407B586-6052-11E9-B3AE-7006E6697425
last_name: Artan
orcid: 0000-0001-8945-6992
- first_name: Stephen
full_name: Barratt, Stephen
id: 57740d2b-2a88-11ec-97cf-d9e6d1b39677
last_name: Barratt
- first_name: Sean M.
full_name: Flynn, Sean M.
last_name: Flynn
- first_name: Farida
full_name: Begum, Farida
last_name: Begum
- first_name: Mark
full_name: Skehel, Mark
last_name: Skehel
- first_name: Armel
full_name: Nicolas, Armel
id: 2A103192-F248-11E8-B48F-1D18A9856A87
last_name: Nicolas
- first_name: Mario
full_name: De Bono, Mario
id: 4E3FF80E-F248-11E8-B48F-1D18A9856A87
last_name: De Bono
orcid: 0000-0001-8347-0443
citation:
ama: Artan M, Barratt S, Flynn SM, et al. Interactome analysis of Caenorhabditis
elegans synapses by TurboID-based proximity labeling. Journal of Biological
Chemistry. 2021;297(3). doi:10.1016/J.JBC.2021.101094
apa: Artan, M., Barratt, S., Flynn, S. M., Begum, F., Skehel, M., Nicolas, A., &
de Bono, M. (2021). Interactome analysis of Caenorhabditis elegans synapses by
TurboID-based proximity labeling. Journal of Biological Chemistry. Elsevier.
https://doi.org/10.1016/J.JBC.2021.101094
chicago: Artan, Murat, Stephen Barratt, Sean M. Flynn, Farida Begum, Mark Skehel,
Armel Nicolas, and Mario de Bono. “Interactome Analysis of Caenorhabditis Elegans
Synapses by TurboID-Based Proximity Labeling.” Journal of Biological Chemistry.
Elsevier, 2021. https://doi.org/10.1016/J.JBC.2021.101094.
ieee: M. Artan et al., “Interactome analysis of Caenorhabditis elegans synapses
by TurboID-based proximity labeling,” Journal of Biological Chemistry,
vol. 297, no. 3. Elsevier, 2021.
ista: Artan M, Barratt S, Flynn SM, Begum F, Skehel M, Nicolas A, de Bono M. 2021.
Interactome analysis of Caenorhabditis elegans synapses by TurboID-based proximity
labeling. Journal of Biological Chemistry. 297(3), 101094.
mla: Artan, Murat, et al. “Interactome Analysis of Caenorhabditis Elegans Synapses
by TurboID-Based Proximity Labeling.” Journal of Biological Chemistry,
vol. 297, no. 3, 101094, Elsevier, 2021, doi:10.1016/J.JBC.2021.101094.
short: M. Artan, S. Barratt, S.M. Flynn, F. Begum, M. Skehel, A. Nicolas, M. de
Bono, Journal of Biological Chemistry 297 (2021).
date_created: 2021-10-10T22:01:23Z
date_published: 2021-09-01T00:00:00Z
date_updated: 2023-08-14T07:24:09Z
day: '01'
ddc:
- '612'
department:
- _id: MaDe
- _id: LifeSc
doi: 10.1016/J.JBC.2021.101094
ec_funded: 1
external_id:
isi:
- '000706409200006'
file:
- access_level: open_access
checksum: 19e39d36c5b9387c6dc0e89c9ae856ab
content_type: application/pdf
creator: cchlebak
date_created: 2021-10-11T12:20:58Z
date_updated: 2021-10-11T12:20:58Z
file_id: '10121'
file_name: 2021_JBC_Artan.pdf
file_size: 1680010
relation: main_file
success: 1
file_date_updated: 2021-10-11T12:20:58Z
has_accepted_license: '1'
intvolume: ' 297'
isi: 1
issue: '3'
language:
- iso: eng
month: '09'
oa: 1
oa_version: Published Version
project:
- _id: 260C2330-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '754411'
name: ISTplus - Postdoctoral Fellowships
publication: Journal of Biological Chemistry
publication_identifier:
eissn:
- 1083-351X
issn:
- 0021-9258
publication_status: published
publisher: Elsevier
quality_controlled: '1'
scopus_import: '1'
status: public
title: Interactome analysis of Caenorhabditis elegans synapses by TurboID-based proximity
labeling
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 297
year: '2021'
...
---
_id: '7800'
abstract:
- lang: eng
text: De novo loss of function mutations in the ubiquitin ligase-encoding gene Cullin3
(CUL3) lead to autism spectrum disorder (ASD). Here, we used Cul3 mouse models
to evaluate the consequences of Cul3 mutations in vivo. Our results show that
Cul3 haploinsufficient mice exhibit deficits in motor coordination as well as
ASD-relevant social and cognitive impairments. Cul3 mutant brain displays cortical
lamination abnormalities due to defective neuronal migration and reduced numbers
of excitatory and inhibitory neurons. In line with the observed abnormal columnar
organization, Cul3 haploinsufficiency is associated with decreased spontaneous
excitatory and inhibitory activity in the cortex. At the molecular level, employing
a quantitative proteomic approach, we show that Cul3 regulates cytoskeletal and
adhesion protein abundance in mouse embryos. Abnormal regulation of cytoskeletal
proteins in Cul3 mutant neuronal cells results in atypical organization of the
actin mesh at the cell leading edge, likely causing the observed migration deficits.
In contrast to these important functions early in development, Cul3 deficiency
appears less relevant at adult stages. In fact, induction of Cul3 haploinsufficiency
in adult mice does not result in the behavioral defects observed in constitutive
Cul3 haploinsufficient animals. Taken together, our data indicate that Cul3 has
a critical role in the regulation of cytoskeletal proteins and neuronal migration
and that ASD-associated defects and behavioral abnormalities are primarily due
to Cul3 functions at early developmental stages.
acknowledged_ssus:
- _id: PreCl
article_processing_charge: No
author:
- first_name: Jasmin
full_name: Morandell, Jasmin
id: 4739D480-F248-11E8-B48F-1D18A9856A87
last_name: Morandell
- first_name: Lena A
full_name: Schwarz, Lena A
id: 29A8453C-F248-11E8-B48F-1D18A9856A87
last_name: Schwarz
- first_name: Bernadette
full_name: Basilico, Bernadette
id: 36035796-5ACA-11E9-A75E-7AF2E5697425
last_name: Basilico
orcid: 0000-0003-1843-3173
- first_name: Saren
full_name: Tasciyan, Saren
id: 4323B49C-F248-11E8-B48F-1D18A9856A87
last_name: Tasciyan
orcid: 0000-0003-1671-393X
- first_name: Armel
full_name: Nicolas, Armel
id: 2A103192-F248-11E8-B48F-1D18A9856A87
last_name: Nicolas
- first_name: Christoph M
full_name: Sommer, Christoph M
id: 4DF26D8C-F248-11E8-B48F-1D18A9856A87
last_name: Sommer
orcid: 0000-0003-1216-9105
- first_name: Caroline
full_name: Kreuzinger, Caroline
id: 382077BA-F248-11E8-B48F-1D18A9856A87
last_name: Kreuzinger
- first_name: Lisa
full_name: Knaus, Lisa
id: 3B2ABCF4-F248-11E8-B48F-1D18A9856A87
last_name: Knaus
- first_name: Zoe
full_name: Dobler, Zoe
id: D23090A2-9057-11EA-883A-A8396FC7A38F
last_name: Dobler
- first_name: Emanuele
full_name: Cacci, Emanuele
last_name: Cacci
- first_name: Johann G
full_name: Danzl, Johann G
id: 42EFD3B6-F248-11E8-B48F-1D18A9856A87
last_name: Danzl
orcid: 0000-0001-8559-3973
- first_name: Gaia
full_name: Novarino, Gaia
id: 3E57A680-F248-11E8-B48F-1D18A9856A87
last_name: Novarino
orcid: 0000-0002-7673-7178
citation:
ama: Morandell J, Schwarz LA, Basilico B, et al. Cul3 regulates cytoskeleton protein
homeostasis and cell migration during a critical window of brain development.
bioRxiv. doi:10.1101/2020.01.10.902064
apa: Morandell, J., Schwarz, L. A., Basilico, B., Tasciyan, S., Nicolas, A., Sommer,
C. M., … Novarino, G. (n.d.). Cul3 regulates cytoskeleton protein homeostasis
and cell migration during a critical window of brain development. bioRxiv.
Cold Spring Harbor Laboratory. https://doi.org/10.1101/2020.01.10.902064
chicago: Morandell, Jasmin, Lena A Schwarz, Bernadette Basilico, Saren Tasciyan,
Armel Nicolas, Christoph M Sommer, Caroline Kreuzinger, et al. “Cul3 Regulates
Cytoskeleton Protein Homeostasis and Cell Migration during a Critical Window of
Brain Development.” BioRxiv. Cold Spring Harbor Laboratory, n.d. https://doi.org/10.1101/2020.01.10.902064 .
ieee: J. Morandell et al., “Cul3 regulates cytoskeleton protein homeostasis
and cell migration during a critical window of brain development,” bioRxiv.
Cold Spring Harbor Laboratory.
ista: Morandell J, Schwarz LA, Basilico B, Tasciyan S, Nicolas A, Sommer CM, Kreuzinger
C, Knaus L, Dobler Z, Cacci E, Danzl JG, Novarino G. Cul3 regulates cytoskeleton
protein homeostasis and cell migration during a critical window of brain development.
bioRxiv, 10.1101/2020.01.10.902064
.
mla: Morandell, Jasmin, et al. “Cul3 Regulates Cytoskeleton Protein Homeostasis
and Cell Migration during a Critical Window of Brain Development.” BioRxiv,
Cold Spring Harbor Laboratory, doi:10.1101/2020.01.10.902064 .
short: J. Morandell, L.A. Schwarz, B. Basilico, S. Tasciyan, A. Nicolas, C.M. Sommer,
C. Kreuzinger, L. Knaus, Z. Dobler, E. Cacci, J.G. Danzl, G. Novarino, BioRxiv
(n.d.).
date_created: 2020-05-05T14:31:33Z
date_published: 2020-01-11T00:00:00Z
date_updated: 2024-09-10T12:04:26Z
day: '11'
ddc:
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department:
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- _id: GaNo
- _id: LifeSc
doi: '10.1101/2020.01.10.902064 '
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month: '01'
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oa_version: Preprint
project:
- _id: 265CB4D0-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: I03600
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publisher: Cold Spring Harbor Laboratory
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critical window of brain development
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legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode
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short: CC BY-NC-ND (4.0)
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---
_id: '6819'
abstract:
- lang: eng
text: Glyphosate (N-phosphonomethyl glycine) and its commercial herbicide formulations
have been shown to exert toxicity via various mechanisms. It has been asserted
that glyphosate substitutes for glycine in polypeptide chains leading to protein
misfolding and toxicity. However, as no direct evidence exists for glycine to
glyphosate substitution in proteins, including in mammalian organisms, we tested
this claim by conducting a proteomics analysis of MDA-MB-231 human breast cancer
cells grown in the presence of 100 mg/L glyphosate for 6 days. Protein extracts
from three treated and three untreated cell cultures were analysed as one TMT-6plex
labelled sample, to highlight a specific pattern (+/+/+/−/−/−) of reporter intensities
for peptides bearing true glyphosate treatment induced-post translational modifications
as well as allowing an investigation of the total proteome.
article_number: '494'
article_processing_charge: No
author:
- first_name: Michael N.
full_name: Antoniou, Michael N.
last_name: Antoniou
- first_name: Armel
full_name: Nicolas, Armel
id: 2A103192-F248-11E8-B48F-1D18A9856A87
last_name: Nicolas
- first_name: Robin
full_name: Mesnage, Robin
last_name: Mesnage
- first_name: Martina
full_name: Biserni, Martina
last_name: Biserni
- first_name: Francesco V.
full_name: Rao, Francesco V.
last_name: Rao
- first_name: Cristina Vazquez
full_name: Martin, Cristina Vazquez
last_name: Martin
citation:
ama: Antoniou MN, Nicolas A, Mesnage R, Biserni M, Rao FV, Martin CV. Glyphosate
does not substitute for glycine in proteins of actively dividing mammalian cells.
BMC Research Notes. 2019;12. doi:10.1186/s13104-019-4534-3
apa: Antoniou, M. N., Nicolas, A., Mesnage, R., Biserni, M., Rao, F. V., & Martin,
C. V. (2019). Glyphosate does not substitute for glycine in proteins of actively
dividing mammalian cells. BMC Research Notes. BioMed Central. https://doi.org/10.1186/s13104-019-4534-3
chicago: Antoniou, Michael N., Armel Nicolas, Robin Mesnage, Martina Biserni, Francesco
V. Rao, and Cristina Vazquez Martin. “Glyphosate Does Not Substitute for Glycine
in Proteins of Actively Dividing Mammalian Cells.” BMC Research Notes.
BioMed Central, 2019. https://doi.org/10.1186/s13104-019-4534-3.
ieee: M. N. Antoniou, A. Nicolas, R. Mesnage, M. Biserni, F. V. Rao, and C. V. Martin,
“Glyphosate does not substitute for glycine in proteins of actively dividing mammalian
cells,” BMC Research Notes, vol. 12. BioMed Central, 2019.
ista: Antoniou MN, Nicolas A, Mesnage R, Biserni M, Rao FV, Martin CV. 2019. Glyphosate
does not substitute for glycine in proteins of actively dividing mammalian cells.
BMC Research Notes. 12, 494.
mla: Antoniou, Michael N., et al. “Glyphosate Does Not Substitute for Glycine in
Proteins of Actively Dividing Mammalian Cells.” BMC Research Notes, vol.
12, 494, BioMed Central, 2019, doi:10.1186/s13104-019-4534-3.
short: M.N. Antoniou, A. Nicolas, R. Mesnage, M. Biserni, F.V. Rao, C.V. Martin,
BMC Research Notes 12 (2019).
date_created: 2019-08-18T22:00:39Z
date_published: 2019-08-08T00:00:00Z
date_updated: 2023-02-23T14:08:14Z
day: '08'
ddc:
- '570'
department:
- _id: LifeSc
doi: 10.1186/s13104-019-4534-3
external_id:
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checksum: 4a2bb7994b7f2c432bf44f5127ea3102
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date_created: 2019-08-23T11:10:35Z
date_updated: 2020-07-14T12:47:40Z
file_id: '6829'
file_name: 2019_BMC_Antoniou.pdf
file_size: 1177482
relation: main_file
file_date_updated: 2020-07-14T12:47:40Z
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intvolume: ' 12'
language:
- iso: eng
month: '08'
oa: 1
oa_version: Published Version
pmid: 1
publication: BMC Research Notes
publication_identifier:
eissn:
- 1756-0500
publication_status: published
publisher: BioMed Central
quality_controlled: '1'
related_material:
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scopus_import: 1
status: public
title: Glyphosate does not substitute for glycine in proteins of actively dividing
mammalian cells
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87
volume: 12
year: '2019'
...
---
_id: '7415'
article_processing_charge: No
article_type: original
author:
- first_name: Jasmin
full_name: Morandell, Jasmin
id: 4739D480-F248-11E8-B48F-1D18A9856A87
last_name: Morandell
- first_name: Armel
full_name: Nicolas, Armel
id: 2A103192-F248-11E8-B48F-1D18A9856A87
last_name: Nicolas
- first_name: Lena A
full_name: Schwarz, Lena A
id: 29A8453C-F248-11E8-B48F-1D18A9856A87
last_name: Schwarz
- first_name: Gaia
full_name: Novarino, Gaia
id: 3E57A680-F248-11E8-B48F-1D18A9856A87
last_name: Novarino
orcid: 0000-0002-7673-7178
citation:
ama: Morandell J, Nicolas A, Schwarz LA, Novarino G. S.16.05 Illuminating the role
of the e3 ubiquitin ligase cullin3 in brain development and autism. European
Neuropsychopharmacology. 2019;29(Supplement 6):S11-S12. doi:10.1016/j.euroneuro.2019.09.040
apa: Morandell, J., Nicolas, A., Schwarz, L. A., & Novarino, G. (2019). S.16.05
Illuminating the role of the e3 ubiquitin ligase cullin3 in brain development
and autism. European Neuropsychopharmacology. Elsevier. https://doi.org/10.1016/j.euroneuro.2019.09.040
chicago: Morandell, Jasmin, Armel Nicolas, Lena A Schwarz, and Gaia Novarino. “S.16.05
Illuminating the Role of the E3 Ubiquitin Ligase Cullin3 in Brain Development
and Autism.” European Neuropsychopharmacology. Elsevier, 2019. https://doi.org/10.1016/j.euroneuro.2019.09.040.
ieee: J. Morandell, A. Nicolas, L. A. Schwarz, and G. Novarino, “S.16.05 Illuminating
the role of the e3 ubiquitin ligase cullin3 in brain development and autism,”
European Neuropsychopharmacology, vol. 29, no. Supplement 6. Elsevier,
pp. S11–S12, 2019.
ista: Morandell J, Nicolas A, Schwarz LA, Novarino G. 2019. S.16.05 Illuminating
the role of the e3 ubiquitin ligase cullin3 in brain development and autism. European
Neuropsychopharmacology. 29(Supplement 6), S11–S12.
mla: Morandell, Jasmin, et al. “S.16.05 Illuminating the Role of the E3 Ubiquitin
Ligase Cullin3 in Brain Development and Autism.” European Neuropsychopharmacology,
vol. 29, no. Supplement 6, Elsevier, 2019, pp. S11–12, doi:10.1016/j.euroneuro.2019.09.040.
short: J. Morandell, A. Nicolas, L.A. Schwarz, G. Novarino, European Neuropsychopharmacology
29 (2019) S11–S12.
date_created: 2020-01-30T10:07:41Z
date_published: 2019-12-13T00:00:00Z
date_updated: 2023-09-07T14:56:17Z
day: '13'
department:
- _id: GaNo
- _id: LifeSc
doi: 10.1016/j.euroneuro.2019.09.040
external_id:
isi:
- '000502657500021'
intvolume: ' 29'
isi: 1
issue: Supplement 6
language:
- iso: eng
month: '12'
oa_version: None
page: S11-S12
publication: European Neuropsychopharmacology
publication_identifier:
issn:
- 0924-977X
publication_status: published
publisher: Elsevier
quality_controlled: '1'
status: public
title: S.16.05 Illuminating the role of the e3 ubiquitin ligase cullin3 in brain development
and autism
type: journal_article
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
volume: 29
year: '2019'
...
---
_id: '9784'
abstract:
- lang: eng
text: 'Additional file 1: Table S1. Kinetics of MDA-MB-231 cell growth in either
the presence or absence of 100Â mg/L glyphosate. Cell counts are given at day-1
of seeding flasks and following 6-days of continuous culture. Note: no differences
in cell numbers were observed between negative control and glyphosate treated
cultures.'
article_processing_charge: No
author:
- first_name: Michael N.
full_name: Antoniou, Michael N.
last_name: Antoniou
- first_name: Armel
full_name: Nicolas, Armel
id: 2A103192-F248-11E8-B48F-1D18A9856A87
last_name: Nicolas
- first_name: Robin
full_name: Mesnage, Robin
last_name: Mesnage
- first_name: Martina
full_name: Biserni, Martina
last_name: Biserni
- first_name: Francesco V.
full_name: Rao, Francesco V.
last_name: Rao
- first_name: Cristina Vazquez
full_name: Martin, Cristina Vazquez
last_name: Martin
citation:
ama: Antoniou MN, Nicolas A, Mesnage R, Biserni M, Rao FV, Martin CV. MOESM1 of
Glyphosate does not substitute for glycine in proteins of actively dividing mammalian
cells. 2019. doi:10.6084/m9.figshare.9411761.v1
apa: Antoniou, M. N., Nicolas, A., Mesnage, R., Biserni, M., Rao, F. V., & Martin,
C. V. (2019). MOESM1 of Glyphosate does not substitute for glycine in proteins
of actively dividing mammalian cells. Springer Nature. https://doi.org/10.6084/m9.figshare.9411761.v1
chicago: Antoniou, Michael N., Armel Nicolas, Robin Mesnage, Martina Biserni, Francesco
V. Rao, and Cristina Vazquez Martin. “MOESM1 of Glyphosate Does Not Substitute
for Glycine in Proteins of Actively Dividing Mammalian Cells.” Springer Nature,
2019. https://doi.org/10.6084/m9.figshare.9411761.v1.
ieee: M. N. Antoniou, A. Nicolas, R. Mesnage, M. Biserni, F. V. Rao, and C. V. Martin,
“MOESM1 of Glyphosate does not substitute for glycine in proteins of actively
dividing mammalian cells.” Springer Nature, 2019.
ista: Antoniou MN, Nicolas A, Mesnage R, Biserni M, Rao FV, Martin CV. 2019. MOESM1
of Glyphosate does not substitute for glycine in proteins of actively dividing
mammalian cells, Springer Nature, 10.6084/m9.figshare.9411761.v1.
mla: Antoniou, Michael N., et al. MOESM1 of Glyphosate Does Not Substitute for
Glycine in Proteins of Actively Dividing Mammalian Cells. Springer Nature,
2019, doi:10.6084/m9.figshare.9411761.v1.
short: M.N. Antoniou, A. Nicolas, R. Mesnage, M. Biserni, F.V. Rao, C.V. Martin,
(2019).
date_created: 2021-08-06T08:14:05Z
date_published: 2019-08-09T00:00:00Z
date_updated: 2023-02-23T12:52:29Z
day: '09'
department:
- _id: LifeSc
doi: 10.6084/m9.figshare.9411761.v1
main_file_link:
- open_access: '1'
url: https://doi.org/10.6084/m9.figshare.9411761.v1
month: '08'
oa: 1
oa_version: Published Version
publisher: Springer Nature
related_material:
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- id: '6819'
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status: public
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...