---
_id: '8674'
abstract:
- lang: eng
text: 'Extrasynaptic actions of glutamate are limited by high-affinity transporters
expressed by perisynaptic astroglial processes (PAPs): this helps maintain point-to-point
transmission in excitatory circuits. Memory formation in the brain is associated
with synaptic remodeling, but how this affects PAPs and therefore extrasynaptic
glutamate actions is poorly understood. Here, we used advanced imaging methods,
in situ and in vivo, to find that a classical synaptic memory mechanism, long-term
potentiation (LTP), triggers withdrawal of PAPs from potentiated synapses. Optical
glutamate sensors combined with patch-clamp and 3D molecular localization reveal
that LTP induction thus prompts spatial retreat of astroglial glutamate transporters,
boosting glutamate spillover and NMDA-receptor-mediated inter-synaptic cross-talk.
The LTP-triggered PAP withdrawal involves NKCC1 transporters and the actin-controlling
protein cofilin but does not depend on major Ca2+-dependent cascades in astrocytes.
We have therefore uncovered a mechanism by which a memory trace at one synapse
could alter signal handling by multiple neighboring connections.'
acknowledgement: We thank J. Angibaud for organotypic cultures and R. Chereau and
J. Tonnesen for help with the STED microscope; also D. Gonzales and the Neurocentre
Magendie INSERM U1215 Genotyping Platform, for breeding management and genotyping.
This work was supported by the Wellcome Trust Principal Fellowships 101896 and 212251,
ERC Advanced Grant 323113, ERC Proof-of-Concept Grant 767372, EC FP7 ITN 606950,
and EU CSA 811011 (D.A.R.); NRW-Rückkehrerpogramm, UCL Excellence Fellowship, German
Research Foundation (DFG) SPP1757 and SFB1089 (C.H.); Human Frontiers Science Program
(C.H., C.J.J., and H.J.); EMBO Long-Term Fellowship (L.B.); Marie Curie FP7 PIRG08-GA-2010-276995
(A.P.), ASTROMODULATION (S.R.); Equipe FRM DEQ 201 303 26519, Conseil Régional d’Aquitaine
R12056GG, INSERM (S.H.R.O.); ANR SUPERTri, ANR Castro (ANR-17-CE16-0002), R-13-BSV4-0007-01,
Université de Bordeaux, labex BRAIN (S.H.R.O. and U.V.N.); CNRS (A.P., S.H.R.O.,
and U.V.N.); HFSP, ANR CEXC, and France-BioImaging ANR-10-INSB-04 (U.V.N.); and
FP7 MemStick Project No. 201600 (M.G.S.).
article_processing_charge: No
article_type: original
author:
- first_name: Christian
full_name: Henneberger, Christian
last_name: Henneberger
- first_name: Lucie
full_name: Bard, Lucie
last_name: Bard
- first_name: Aude
full_name: Panatier, Aude
last_name: Panatier
- first_name: James P.
full_name: Reynolds, James P.
last_name: Reynolds
- first_name: Olga
full_name: Kopach, Olga
last_name: Kopach
- first_name: Nikolay I.
full_name: Medvedev, Nikolay I.
last_name: Medvedev
- first_name: Daniel
full_name: Minge, Daniel
last_name: Minge
- first_name: Michel K.
full_name: Herde, Michel K.
last_name: Herde
- first_name: Stefanie
full_name: Anders, Stefanie
last_name: Anders
- first_name: Igor
full_name: Kraev, Igor
last_name: Kraev
- first_name: Janosch P.
full_name: Heller, Janosch P.
last_name: Heller
- first_name: Sylvain
full_name: Rama, Sylvain
last_name: Rama
- first_name: Kaiyu
full_name: Zheng, Kaiyu
last_name: Zheng
- first_name: Thomas P.
full_name: Jensen, Thomas P.
last_name: Jensen
- first_name: Inmaculada
full_name: Sanchez-Romero, Inmaculada
id: 3D9C5D30-F248-11E8-B48F-1D18A9856A87
last_name: Sanchez-Romero
- first_name: Colin J.
full_name: Jackson, Colin J.
last_name: Jackson
- first_name: Harald L
full_name: Janovjak, Harald L
id: 33BA6C30-F248-11E8-B48F-1D18A9856A87
last_name: Janovjak
orcid: 0000-0002-8023-9315
- first_name: Ole Petter
full_name: Ottersen, Ole Petter
last_name: Ottersen
- first_name: Erlend Arnulf
full_name: Nagelhus, Erlend Arnulf
last_name: Nagelhus
- first_name: Stephane H.R.
full_name: Oliet, Stephane H.R.
last_name: Oliet
- first_name: Michael G.
full_name: Stewart, Michael G.
last_name: Stewart
- first_name: U. VAlentin
full_name: Nägerl, U. VAlentin
last_name: Nägerl
- first_name: 'Dmitri A. '
full_name: 'Rusakov, Dmitri A. '
last_name: Rusakov
citation:
ama: Henneberger C, Bard L, Panatier A, et al. LTP induction boosts glutamate spillover
by driving withdrawal of perisynaptic astroglia. Neuron. 2020;108(5):P919-936.E11.
doi:10.1016/j.neuron.2020.08.030
apa: Henneberger, C., Bard, L., Panatier, A., Reynolds, J. P., Kopach, O., Medvedev,
N. I., … Rusakov, D. A. (2020). LTP induction boosts glutamate spillover by driving
withdrawal of perisynaptic astroglia. Neuron. Elsevier. https://doi.org/10.1016/j.neuron.2020.08.030
chicago: Henneberger, Christian, Lucie Bard, Aude Panatier, James P. Reynolds, Olga
Kopach, Nikolay I. Medvedev, Daniel Minge, et al. “LTP Induction Boosts Glutamate
Spillover by Driving Withdrawal of Perisynaptic Astroglia.” Neuron. Elsevier,
2020. https://doi.org/10.1016/j.neuron.2020.08.030.
ieee: C. Henneberger et al., “LTP induction boosts glutamate spillover by
driving withdrawal of perisynaptic astroglia,” Neuron, vol. 108, no. 5.
Elsevier, p. P919–936.E11, 2020.
ista: Henneberger C, Bard L, Panatier A, Reynolds JP, Kopach O, Medvedev NI, Minge
D, Herde MK, Anders S, Kraev I, Heller JP, Rama S, Zheng K, Jensen TP, Sanchez-Romero
I, Jackson CJ, Janovjak HL, Ottersen OP, Nagelhus EA, Oliet SHR, Stewart MG, Nägerl
UVa, Rusakov DA. 2020. LTP induction boosts glutamate spillover by driving withdrawal
of perisynaptic astroglia. Neuron. 108(5), P919–936.E11.
mla: Henneberger, Christian, et al. “LTP Induction Boosts Glutamate Spillover by
Driving Withdrawal of Perisynaptic Astroglia.” Neuron, vol. 108, no. 5,
Elsevier, 2020, p. P919–936.E11, doi:10.1016/j.neuron.2020.08.030.
short: C. Henneberger, L. Bard, A. Panatier, J.P. Reynolds, O. Kopach, N.I. Medvedev,
D. Minge, M.K. Herde, S. Anders, I. Kraev, J.P. Heller, S. Rama, K. Zheng, T.P.
Jensen, I. Sanchez-Romero, C.J. Jackson, H.L. Janovjak, O.P. Ottersen, E.A. Nagelhus,
S.H.R. Oliet, M.G. Stewart, U.Va. Nägerl, D.A. Rusakov, Neuron 108 (2020) P919–936.E11.
date_created: 2020-10-18T22:01:38Z
date_published: 2020-12-09T00:00:00Z
date_updated: 2023-08-22T09:59:29Z
day: '09'
ddc:
- '570'
department:
- _id: HaJa
doi: 10.1016/j.neuron.2020.08.030
external_id:
isi:
- '000603428000010'
pmid:
- '32976770'
file:
- access_level: open_access
checksum: 054562bb50165ef9a1f46631c1c5e36b
content_type: application/pdf
creator: dernst
date_created: 2020-12-10T14:42:09Z
date_updated: 2020-12-10T14:42:09Z
file_id: '8939'
file_name: 2020_Neuron_Henneberger.pdf
file_size: 7518960
relation: main_file
success: 1
file_date_updated: 2020-12-10T14:42:09Z
has_accepted_license: '1'
intvolume: ' 108'
isi: 1
issue: '5'
language:
- iso: eng
month: '12'
oa: 1
oa_version: Published Version
page: P919-936.E11
pmid: 1
publication: Neuron
publication_identifier:
eissn:
- '10974199'
issn:
- '08966273'
publication_status: published
publisher: Elsevier
quality_controlled: '1'
scopus_import: '1'
status: public
title: LTP induction boosts glutamate spillover by driving withdrawal of perisynaptic
astroglia
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: 108
year: '2020'
...
---
_id: '5984'
abstract:
- lang: eng
text: G-protein-coupled receptors (GPCRs) form the largest receptor family, relay
environmental stimuli to changes in cell behavior and represent prime drug targets.
Many GPCRs are classified as orphan receptors because of the limited knowledge
on their ligands and coupling to cellular signaling machineries. Here, we engineer
a library of 63 chimeric receptors that contain the signaling domains of human
orphan and understudied GPCRs functionally linked to the light-sensing domain
of rhodopsin. Upon stimulation with visible light, we identify activation of canonical
cell signaling pathways, including cAMP-, Ca2+-, MAPK/ERK-, and Rho-dependent
pathways, downstream of the engineered receptors. For the human pseudogene GPR33,
we resurrect a signaling function that supports its hypothesized role as a pathogen
entry site. These results demonstrate that substituting unknown chemical activators
with a light switch can reveal information about protein function and provide
an optically controlled protein library for exploring the physiology and therapeutic
potential of understudied GPCRs.
article_number: '1950'
article_processing_charge: No
author:
- first_name: Maurizio
full_name: Morri, Maurizio
id: 4863116E-F248-11E8-B48F-1D18A9856A87
last_name: Morri
- first_name: Inmaculada
full_name: Sanchez-Romero, Inmaculada
id: 3D9C5D30-F248-11E8-B48F-1D18A9856A87
last_name: Sanchez-Romero
- first_name: Alexandra-Madelaine
full_name: Tichy, Alexandra-Madelaine
id: 29D8BB2C-F248-11E8-B48F-1D18A9856A87
last_name: Tichy
- first_name: Stephanie
full_name: Kainrath, Stephanie
id: 32CFBA64-F248-11E8-B48F-1D18A9856A87
last_name: Kainrath
- first_name: Elliot J.
full_name: Gerrard, Elliot J.
last_name: Gerrard
- first_name: Priscila
full_name: Hirschfeld, Priscila
id: 435ACB3A-F248-11E8-B48F-1D18A9856A87
last_name: Hirschfeld
- first_name: Jan
full_name: Schwarz, Jan
id: 346C1EC6-F248-11E8-B48F-1D18A9856A87
last_name: Schwarz
- first_name: Harald L
full_name: Janovjak, Harald L
id: 33BA6C30-F248-11E8-B48F-1D18A9856A87
last_name: Janovjak
orcid: 0000-0002-8023-9315
citation:
ama: Morri M, Sanchez-Romero I, Tichy A-M, et al. Optical functionalization of human
class A orphan G-protein-coupled receptors. Nature Communications. 2018;9(1).
doi:10.1038/s41467-018-04342-1
apa: Morri, M., Sanchez-Romero, I., Tichy, A.-M., Kainrath, S., Gerrard, E. J.,
Hirschfeld, P., … Janovjak, H. L. (2018). Optical functionalization of human class
A orphan G-protein-coupled receptors. Nature Communications. Springer Nature.
https://doi.org/10.1038/s41467-018-04342-1
chicago: Morri, Maurizio, Inmaculada Sanchez-Romero, Alexandra-Madelaine Tichy,
Stephanie Kainrath, Elliot J. Gerrard, Priscila Hirschfeld, Jan Schwarz, and Harald
L Janovjak. “Optical Functionalization of Human Class A Orphan G-Protein-Coupled
Receptors.” Nature Communications. Springer Nature, 2018. https://doi.org/10.1038/s41467-018-04342-1.
ieee: M. Morri et al., “Optical functionalization of human class A orphan
G-protein-coupled receptors,” Nature Communications, vol. 9, no. 1. Springer
Nature, 2018.
ista: Morri M, Sanchez-Romero I, Tichy A-M, Kainrath S, Gerrard EJ, Hirschfeld P,
Schwarz J, Janovjak HL. 2018. Optical functionalization of human class A orphan
G-protein-coupled receptors. Nature Communications. 9(1), 1950.
mla: Morri, Maurizio, et al. “Optical Functionalization of Human Class A Orphan
G-Protein-Coupled Receptors.” Nature Communications, vol. 9, no. 1, 1950,
Springer Nature, 2018, doi:10.1038/s41467-018-04342-1.
short: M. Morri, I. Sanchez-Romero, A.-M. Tichy, S. Kainrath, E.J. Gerrard, P. Hirschfeld,
J. Schwarz, H.L. Janovjak, Nature Communications 9 (2018).
date_created: 2019-02-14T10:50:24Z
date_published: 2018-12-01T00:00:00Z
date_updated: 2023-09-19T14:29:32Z
day: '01'
ddc:
- '570'
department:
- _id: HaJa
- _id: CaGu
- _id: MiSi
doi: 10.1038/s41467-018-04342-1
ec_funded: 1
external_id:
isi:
- '000432280000006'
file:
- access_level: open_access
checksum: 8325fcc194264af4749e662a73bf66b5
content_type: application/pdf
creator: kschuh
date_created: 2019-02-14T10:58:29Z
date_updated: 2020-07-14T12:47:14Z
file_id: '5985'
file_name: 2018_Springer_Morri.pdf
file_size: 1349914
relation: main_file
file_date_updated: 2020-07-14T12:47:14Z
has_accepted_license: '1'
intvolume: ' 9'
isi: 1
issue: '1'
language:
- iso: eng
month: '12'
oa: 1
oa_version: Published Version
project:
- _id: 25548C20-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '303564'
name: Microbial Ion Channels for Synthetic Neurobiology
- _id: 255A6082-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: W1232-B24
name: Molecular Drug Targets
publication: Nature Communications
publication_identifier:
issn:
- 2041-1723
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
scopus_import: '1'
status: public
title: Optical functionalization of human class A orphan G-protein-coupled receptors
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: c635000d-4b10-11ee-a964-aac5a93f6ac1
volume: 9
year: '2018'
...
---
_id: '137'
abstract:
- lang: eng
text: Fluorescent sensors are an essential part of the experimental toolbox of the
life sciences, where they are used ubiquitously to visualize intra- and extracellular
signaling. In the brain, optical neurotransmitter sensors can shed light on temporal
and spatial aspects of signal transmission by directly observing, for instance,
neurotransmitter release and spread. Here we report the development and application
of the first optical sensor for the amino acid glycine, which is both an inhibitory
neurotransmitter and a co-agonist of the N-methyl-d-aspartate receptors (NMDARs)
involved in synaptic plasticity. Computational design of a glycine-specific binding
protein allowed us to produce the optical glycine FRET sensor (GlyFS), which can
be used with single and two-photon excitation fluorescence microscopy. We took
advantage of this newly developed sensor to test predictions about the uneven
spatial distribution of glycine in extracellular space and to demonstrate that
extracellular glycine levels are controlled by plasticity-inducing stimuli.
article_processing_charge: No
article_type: original
author:
- first_name: William
full_name: Zhang, William
last_name: Zhang
- first_name: Michel
full_name: Herde, Michel
last_name: Herde
- first_name: Joshua
full_name: Mitchell, Joshua
last_name: Mitchell
- first_name: Jason
full_name: Whitfield, Jason
last_name: Whitfield
- first_name: Andreas
full_name: Wulff, Andreas
last_name: Wulff
- first_name: Vanessa
full_name: Vongsouthi, Vanessa
last_name: Vongsouthi
- first_name: Inmaculada
full_name: Sanchez Romero, Inmaculada
id: 3D9C5D30-F248-11E8-B48F-1D18A9856A87
last_name: Sanchez Romero
- first_name: Polina
full_name: Gulakova, Polina
last_name: Gulakova
- first_name: Daniel
full_name: Minge, Daniel
last_name: Minge
- first_name: Björn
full_name: Breithausen, Björn
last_name: Breithausen
- first_name: Susanne
full_name: Schoch, Susanne
last_name: Schoch
- first_name: Harald L
full_name: Janovjak, Harald L
id: 33BA6C30-F248-11E8-B48F-1D18A9856A87
last_name: Janovjak
orcid: 0000-0002-8023-9315
- first_name: Colin
full_name: Jackson, Colin
last_name: Jackson
- first_name: Christian
full_name: Henneberger, Christian
last_name: Henneberger
citation:
ama: Zhang W, Herde M, Mitchell J, et al. Monitoring hippocampal glycine with the
computationally designed optical sensor GlyFS. Nature Chemical Biology.
2018;14(9):861-869. doi:10.1038/s41589-018-0108-2
apa: Zhang, W., Herde, M., Mitchell, J., Whitfield, J., Wulff, A., Vongsouthi, V.,
… Henneberger, C. (2018). Monitoring hippocampal glycine with the computationally
designed optical sensor GlyFS. Nature Chemical Biology. Nature Publishing
Group. https://doi.org/10.1038/s41589-018-0108-2
chicago: Zhang, William, Michel Herde, Joshua Mitchell, Jason Whitfield, Andreas
Wulff, Vanessa Vongsouthi, Inmaculada Sanchez-Romero, et al. “Monitoring Hippocampal
Glycine with the Computationally Designed Optical Sensor GlyFS.” Nature Chemical
Biology. Nature Publishing Group, 2018. https://doi.org/10.1038/s41589-018-0108-2.
ieee: W. Zhang et al., “Monitoring hippocampal glycine with the computationally
designed optical sensor GlyFS,” Nature Chemical Biology, vol. 14, no. 9.
Nature Publishing Group, pp. 861–869, 2018.
ista: Zhang W, Herde M, Mitchell J, Whitfield J, Wulff A, Vongsouthi V, Sanchez-Romero
I, Gulakova P, Minge D, Breithausen B, Schoch S, Janovjak HL, Jackson C, Henneberger
C. 2018. Monitoring hippocampal glycine with the computationally designed optical
sensor GlyFS. Nature Chemical Biology. 14(9), 861–869.
mla: Zhang, William, et al. “Monitoring Hippocampal Glycine with the Computationally
Designed Optical Sensor GlyFS.” Nature Chemical Biology, vol. 14, no. 9,
Nature Publishing Group, 2018, pp. 861–69, doi:10.1038/s41589-018-0108-2.
short: W. Zhang, M. Herde, J. Mitchell, J. Whitfield, A. Wulff, V. Vongsouthi, I.
Sanchez-Romero, P. Gulakova, D. Minge, B. Breithausen, S. Schoch, H.L. Janovjak,
C. Jackson, C. Henneberger, Nature Chemical Biology 14 (2018) 861–869.
date_created: 2018-12-11T11:44:49Z
date_published: 2018-07-30T00:00:00Z
date_updated: 2023-09-13T08:58:05Z
day: '30'
department:
- _id: HaJa
doi: 10.1038/s41589-018-0108-2
external_id:
isi:
- '000442174500013'
pmid:
- '30061718 '
intvolume: ' 14'
isi: 1
issue: '9'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://www.ncbi.nlm.nih.gov/pubmed/30061718
month: '07'
oa: 1
oa_version: Submitted Version
page: 861 - 869
pmid: 1
project:
- _id: 255BFFFA-B435-11E9-9278-68D0E5697425
grant_number: RGY0084/2012
name: In situ real-time imaging of neurotransmitter signaling using designer optical
sensors (HFSP Young Investigator)
publication: Nature Chemical Biology
publication_status: published
publisher: Nature Publishing Group
publist_id: '7786'
quality_controlled: '1'
scopus_import: '1'
status: public
title: Monitoring hippocampal glycine with the computationally designed optical sensor
GlyFS
type: journal_article
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
volume: 14
year: '2018'
...
---
_id: '957'
abstract:
- lang: eng
text: Small molecule biosensors based on Forster resonance energy transfer (FRET)
enable small molecule signaling to be monitored with high spatial and temporal
resolution in complex cellular environments. FRET sensors can be constructed by
fusing a pair of fluorescent proteins to a suitable recognition domain, such as
a member of the solute-binding protein (SBP) superfamily. However, naturally occurring
SBPs may be unsuitable for incorporation into FRET sensors due to their low thermostability,
which may preclude imaging under physiological conditions, or because the positions
of their N- and C-termini may be suboptimal for fusion of fluorescent proteins,
which may limit the dynamic range of the resulting sensors. Here, we show how
these problems can be overcome using ancestral protein reconstruction and circular
permutation. Ancestral protein reconstruction, used as a protein engineering strategy,
leverages phylogenetic information to improve the thermostability of proteins,
while circular permutation enables the termini of an SBP to be repositioned to
maximize the dynamic range of the resulting FRET sensor. We also provide a protocol
for cloning the engineered SBPs into FRET sensor constructs using Golden Gate
assembly and discuss considerations for in situ characterization of the FRET sensors.
alternative_title:
- Methods in Molecular Biology
author:
- first_name: Ben
full_name: Clifton, Ben
last_name: Clifton
- first_name: Jason
full_name: Whitfield, Jason
last_name: Whitfield
- first_name: Inmaculada
full_name: Sanchez Romero, Inmaculada
id: 3D9C5D30-F248-11E8-B48F-1D18A9856A87
last_name: Sanchez Romero
- first_name: Michel
full_name: Herde, Michel
last_name: Herde
- first_name: Christian
full_name: Henneberger, Christian
last_name: Henneberger
- first_name: Harald L
full_name: Janovjak, Harald L
id: 33BA6C30-F248-11E8-B48F-1D18A9856A87
last_name: Janovjak
orcid: 0000-0002-8023-9315
- first_name: Colin
full_name: Jackson, Colin
last_name: Jackson
citation:
ama: 'Clifton B, Whitfield J, Sanchez-Romero I, et al. Ancestral protein reconstruction
and circular permutation for improving the stability and dynamic range of FRET
sensors. In: Stein V, ed. Synthetic Protein Switches. Vol 1596. Synthetic
Protein Switches. Springer; 2017:71-87. doi:10.1007/978-1-4939-6940-1_5'
apa: Clifton, B., Whitfield, J., Sanchez-Romero, I., Herde, M., Henneberger, C.,
Janovjak, H. L., & Jackson, C. (2017). Ancestral protein reconstruction and
circular permutation for improving the stability and dynamic range of FRET sensors.
In V. Stein (Ed.), Synthetic Protein Switches (Vol. 1596, pp. 71–87). Springer.
https://doi.org/10.1007/978-1-4939-6940-1_5
chicago: Clifton, Ben, Jason Whitfield, Inmaculada Sanchez-Romero, Michel Herde,
Christian Henneberger, Harald L Janovjak, and Colin Jackson. “Ancestral Protein
Reconstruction and Circular Permutation for Improving the Stability and Dynamic
Range of FRET Sensors.” In Synthetic Protein Switches, edited by Viktor
Stein, 1596:71–87. Synthetic Protein Switches. Springer, 2017. https://doi.org/10.1007/978-1-4939-6940-1_5.
ieee: B. Clifton et al., “Ancestral protein reconstruction and circular permutation
for improving the stability and dynamic range of FRET sensors,” in Synthetic
Protein Switches, vol. 1596, V. Stein, Ed. Springer, 2017, pp. 71–87.
ista: 'Clifton B, Whitfield J, Sanchez-Romero I, Herde M, Henneberger C, Janovjak
HL, Jackson C. 2017.Ancestral protein reconstruction and circular permutation
for improving the stability and dynamic range of FRET sensors. In: Synthetic Protein
Switches. Methods in Molecular Biology, vol. 1596, 71–87.'
mla: Clifton, Ben, et al. “Ancestral Protein Reconstruction and Circular Permutation
for Improving the Stability and Dynamic Range of FRET Sensors.” Synthetic Protein
Switches, edited by Viktor Stein, vol. 1596, Springer, 2017, pp. 71–87, doi:10.1007/978-1-4939-6940-1_5.
short: B. Clifton, J. Whitfield, I. Sanchez-Romero, M. Herde, C. Henneberger, H.L.
Janovjak, C. Jackson, in:, V. Stein (Ed.), Synthetic Protein Switches, Springer,
2017, pp. 71–87.
date_created: 2018-12-11T11:49:24Z
date_published: 2017-03-15T00:00:00Z
date_updated: 2021-01-12T08:22:13Z
day: '15'
department:
- _id: HaJa
doi: 10.1007/978-1-4939-6940-1_5
editor:
- first_name: Viktor
full_name: Stein, Viktor
last_name: Stein
intvolume: ' 1596'
language:
- iso: eng
month: '03'
oa_version: None
page: 71 - 87
project:
- _id: 255BFFFA-B435-11E9-9278-68D0E5697425
grant_number: RGY0084/2012
name: In situ real-time imaging of neurotransmitter signaling using designer optical
sensors (HFSP Young Investigator)
publication: Synthetic Protein Switches
publication_identifier:
issn:
- '10643745'
publication_status: published
publisher: Springer
publist_id: '6451'
quality_controlled: '1'
scopus_import: 1
series_title: Synthetic Protein Switches
status: public
title: Ancestral protein reconstruction and circular permutation for improving the
stability and dynamic range of FRET sensors
type: book_chapter
user_id: 4435EBFC-F248-11E8-B48F-1D18A9856A87
volume: 1596
year: '2017'
...
---
_id: '1549'
abstract:
- lang: eng
text: Nature has incorporated small photochromic molecules, colloquially termed
'photoswitches', in photoreceptor proteins to sense optical cues in photo-taxis
and vision. While Nature's ability to employ light-responsive functionalities
has long been recognized, it was not until recently that scientists designed,
synthesized and applied synthetic photochromes to manipulate many of which open
rapidly and locally in their native cell types, biological processes with the
temporal and spatial resolution of light. Ion channels in particular have come
to the forefront of proteins that can be put under the designer control of synthetic
photochromes. Photochromic ion channel controllers are comprised of three classes,
photochromic soluble ligands (PCLs), photochromic tethered ligands (PTLs) and
photochromic crosslinkers (PXs), and in each class ion channel functionality is
controlled through reversible changes in photochrome structure. By acting as light-dependent
ion channel agonists, antagonist or modulators, photochromic controllers effectively
converted a wide range of ion channels, including voltage-gated ion channels,
'leak channels', tri-, tetra- and pentameric ligand-gated ion channels, and temperaturesensitive
ion channels, into man-made photoreceptors. Control by photochromes can be reversible,
unlike in the case of 'caged' compounds, and non-invasive with high spatial precision,
unlike pharmacology and electrical manipulation. Here, we introduce design principles
of emerging photochromic molecules that act on ion channels and discuss the impact
that these molecules are beginning to have on ion channel biophysics and neuronal
physiology.
author:
- first_name: Catherine
full_name: Mckenzie, Catherine
id: 3EEDE19A-F248-11E8-B48F-1D18A9856A87
last_name: Mckenzie
- first_name: Inmaculada
full_name: Sanchez Romero, Inmaculada
id: 3D9C5D30-F248-11E8-B48F-1D18A9856A87
last_name: Sanchez Romero
- first_name: Harald L
full_name: Janovjak, Harald L
id: 33BA6C30-F248-11E8-B48F-1D18A9856A87
last_name: Janovjak
orcid: 0000-0002-8023-9315
citation:
ama: 'Mckenzie C, Sanchez-Romero I, Janovjak HL. Flipping the photoswitch: Ion channels
under light control. In: Novel Chemical Tools to Study Ion Channel Biology.
Vol 869. Advances in Experimental Medicine and Biology. Springer; 2015:101-117.
doi:10.1007/978-1-4939-2845-3_6'
apa: 'Mckenzie, C., Sanchez-Romero, I., & Janovjak, H. L. (2015). Flipping the
photoswitch: Ion channels under light control. In Novel chemical tools to study
ion channel biology (Vol. 869, pp. 101–117). Springer. https://doi.org/10.1007/978-1-4939-2845-3_6'
chicago: 'Mckenzie, Catherine, Inmaculada Sanchez-Romero, and Harald L Janovjak.
“Flipping the Photoswitch: Ion Channels under Light Control.” In Novel Chemical
Tools to Study Ion Channel Biology, 869:101–17. Advances in Experimental Medicine
and Biology. Springer, 2015. https://doi.org/10.1007/978-1-4939-2845-3_6.'
ieee: 'C. Mckenzie, I. Sanchez-Romero, and H. L. Janovjak, “Flipping the photoswitch:
Ion channels under light control,” in Novel chemical tools to study ion channel
biology, vol. 869, Springer, 2015, pp. 101–117.'
ista: 'Mckenzie C, Sanchez-Romero I, Janovjak HL. 2015.Flipping the photoswitch:
Ion channels under light control. In: Novel chemical tools to study ion channel
biology. vol. 869, 101–117.'
mla: 'Mckenzie, Catherine, et al. “Flipping the Photoswitch: Ion Channels under
Light Control.” Novel Chemical Tools to Study Ion Channel Biology, vol.
869, Springer, 2015, pp. 101–17, doi:10.1007/978-1-4939-2845-3_6.'
short: C. Mckenzie, I. Sanchez-Romero, H.L. Janovjak, in:, Novel Chemical Tools
to Study Ion Channel Biology, Springer, 2015, pp. 101–117.
date_created: 2018-12-11T11:52:39Z
date_published: 2015-09-18T00:00:00Z
date_updated: 2021-01-12T06:51:32Z
day: '18'
ddc:
- '571'
- '576'
department:
- _id: HaJa
doi: 10.1007/978-1-4939-2845-3_6
file:
- access_level: open_access
checksum: bd1bfdf2423a0c3b6e7cabfa8b44bc0f
content_type: application/pdf
creator: system
date_created: 2018-12-12T10:11:02Z
date_updated: 2020-07-14T12:45:01Z
file_id: '4854'
file_name: IST-2017-839-v1+1_mckenzie.pdf
file_size: 1919655
relation: main_file
file_date_updated: 2020-07-14T12:45:01Z
has_accepted_license: '1'
intvolume: ' 869'
language:
- iso: eng
month: '09'
oa: 1
oa_version: Submitted Version
page: 101 - 117
publication: Novel chemical tools to study ion channel biology
publication_identifier:
isbn:
- 978-1-4939-2844-6
publication_status: published
publisher: Springer
publist_id: '5622'
pubrep_id: '839'
quality_controlled: '1'
scopus_import: 1
series_title: Advances in Experimental Medicine and Biology
status: public
title: 'Flipping the photoswitch: Ion channels under light control'
type: book_chapter
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 869
year: '2015'
...
---
_id: '2471'
abstract:
- lang: eng
text: The impact of disulfide bonds on protein stability goes beyond simple equilibrium
thermodynamics effects associated with the conformational entropy of the unfolded
state. Indeed, disulfide crosslinks may play a role in the prevention of dysfunctional
association and strongly affect the rates of irreversible enzyme inactivation,
highly relevant in biotechnological applications. While these kinetic-stability
effects remain poorly understood, by analogy with proposed mechanisms for processes
of protein aggregation and fibrillogenesis, we propose that they may be determined
by the properties of sparsely-populated, partially-unfolded intermediates. Here
we report the successful design, on the basis of high temperature molecular-dynamics
simulations, of six thermodynamically and kinetically stabilized variants of phytase
from Citrobacter braakii (a biotechnologically important enzyme) with one, two
or three engineered disulfides. Activity measurements and 3D crystal structure
determination demonstrate that the engineered crosslinks do not cause dramatic
alterations in the native structure. The inactivation kinetics for all the variants
displays a strongly non-Arrhenius temperature dependence, with the time-scale
for the irreversible denaturation process reaching a minimum at a given temperature
within the range of the denaturation transition. We show this striking feature
to be a signature of a key role played by a partially unfolded, intermediate state/ensemble.
Energetic and mutational analyses confirm that the intermediate is highly unfolded
(akin to a proposed critical intermediate in the misfolding of the prion protein),
a result that explains the observed kinetic stabilization. Our results provide
a rationale for the kinetic-stability consequences of disulfide-crosslink engineering
and an experimental methodology to arrive at energetic/structural descriptions
of the sparsely populated and elusive intermediates that play key roles in irreversible
protein denaturation.
article_number: e70013
author:
- first_name: Inmaculada
full_name: Sanchez Romero, Inmaculada
id: 3D9C5D30-F248-11E8-B48F-1D18A9856A87
last_name: Sanchez Romero
- first_name: Antonio
full_name: Ariza, Antonio
last_name: Ariza
- first_name: Keith
full_name: Wilson, Keith
last_name: Wilson
- first_name: Michael
full_name: Skjøt, Michael
last_name: Skjøt
- first_name: Jesper
full_name: Vind, Jesper
last_name: Vind
- first_name: Leonardo
full_name: De Maria, Leonardo
last_name: De Maria
- first_name: Lars
full_name: Skov, Lars
last_name: Skov
- first_name: Jose
full_name: Sánchez Ruiz, Jose
last_name: Sánchez Ruiz
citation:
ama: Sanchez-Romero I, Ariza A, Wilson K, et al. Mechanism of protein kinetic stabilization
by engineered disulfide crosslinks. PLoS One. 2013;8(7). doi:10.1371/journal.pone.0070013
apa: Sanchez-Romero, I., Ariza, A., Wilson, K., Skjøt, M., Vind, J., De Maria, L.,
… Sánchez Ruiz, J. (2013). Mechanism of protein kinetic stabilization by engineered
disulfide crosslinks. PLoS One. Public Library of Science. https://doi.org/10.1371/journal.pone.0070013
chicago: Sanchez-Romero, Inmaculada, Antonio Ariza, Keith Wilson, Michael Skjøt,
Jesper Vind, Leonardo De Maria, Lars Skov, and Jose Sánchez Ruiz. “Mechanism of
Protein Kinetic Stabilization by Engineered Disulfide Crosslinks.” PLoS One.
Public Library of Science, 2013. https://doi.org/10.1371/journal.pone.0070013.
ieee: I. Sanchez-Romero et al., “Mechanism of protein kinetic stabilization
by engineered disulfide crosslinks,” PLoS One, vol. 8, no. 7. Public Library
of Science, 2013.
ista: Sanchez-Romero I, Ariza A, Wilson K, Skjøt M, Vind J, De Maria L, Skov L,
Sánchez Ruiz J. 2013. Mechanism of protein kinetic stabilization by engineered
disulfide crosslinks. PLoS One. 8(7), e70013.
mla: Sanchez-Romero, Inmaculada, et al. “Mechanism of Protein Kinetic Stabilization
by Engineered Disulfide Crosslinks.” PLoS One, vol. 8, no. 7, e70013, Public
Library of Science, 2013, doi:10.1371/journal.pone.0070013.
short: I. Sanchez-Romero, A. Ariza, K. Wilson, M. Skjøt, J. Vind, L. De Maria, L.
Skov, J. Sánchez Ruiz, PLoS One 8 (2013).
date_created: 2018-12-11T11:57:51Z
date_published: 2013-07-30T00:00:00Z
date_updated: 2021-01-12T06:57:41Z
day: '30'
ddc:
- '570'
department:
- _id: HaJa
doi: 10.1371/journal.pone.0070013
file:
- access_level: open_access
checksum: c0c96cc76ed7ef0d036a31a7e33c9a37
content_type: application/pdf
creator: system
date_created: 2018-12-12T10:15:07Z
date_updated: 2020-07-14T12:45:41Z
file_id: '5124'
file_name: IST-2016-414-v1+1_journal.pone.0070013.pdf
file_size: 1323666
relation: main_file
file_date_updated: 2020-07-14T12:45:41Z
has_accepted_license: '1'
intvolume: ' 8'
issue: '7'
language:
- iso: eng
month: '07'
oa: 1
oa_version: Published Version
publication: PLoS One
publication_status: published
publisher: Public Library of Science
publist_id: '4430'
pubrep_id: '414'
quality_controlled: '1'
scopus_import: 1
status: public
title: Mechanism of protein kinetic stabilization by engineered disulfide crosslinks
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: 8
year: '2013'
...