---
_id: '679'
abstract:
- lang: eng
text: Protective responses against pathogens require a rapid mobilization of resting
neutrophils and the timely removal of activated ones. Neutrophils are exceptionally
short-lived leukocytes, yet it remains unclear whether the lifespan of pathogen-engaged
neutrophils is regulated differently from that in the circulating steady-state
pool. Here, we have found that under homeostatic conditions, the mRNA-destabilizing
protein tristetraprolin (TTP) regulates apoptosis and the numbers of activated
infiltrating murine neutrophils but not neutrophil cellularity. Activated TTP-deficient
neutrophils exhibited decreased apoptosis and enhanced accumulation at the infection
site. In the context of myeloid-specific deletion of Ttp, the potentiation of
neutrophil deployment protected mice against lethal soft tissue infection with
Streptococcus pyogenes and prevented bacterial dissemination. Neutrophil transcriptome
analysis revealed that decreased apoptosis of TTP-deficient neutrophils was specifically
associated with elevated expression of myeloid cell leukemia 1 (Mcl1) but not
other antiapoptotic B cell leukemia/ lymphoma 2 (Bcl2) family members. Higher
Mcl1 expression resulted from stabilization of Mcl1 mRNA in the absence of TTP.
The low apoptosis rate of infiltrating TTP-deficient neutrophils was comparable
to that of transgenic Mcl1-overexpressing neutrophils. Our study demonstrates
that posttranscriptional gene regulation by TTP schedules the termination of the
antimicrobial engagement of neutrophils. The balancing role of TTP comes at the
cost of an increased risk of bacterial infections.
acknowledgement: This work was supported by grants from the Austrian Science Fund
(FWF) (P27538-B21, I1621-B22, and SFB 43, to PK); by funding from the European Union
Seventh Framework Programme Marie Curie Initial Training Networks (FP7-PEOPLE-2012-ITN)
for the project INBIONET (INfection BIOlogy Training NETwork under grant agreement
PITN-GA-2012-316682; and by a joint research cluster initiative of the University
of Vienna and the Medical University of Vienna.
author:
- first_name: Florian
full_name: Ebner, Florian
last_name: Ebner
- first_name: Vitaly
full_name: Sedlyarov, Vitaly
last_name: Sedlyarov
- first_name: Saren
full_name: Tasciyan, Saren
id: 4323B49C-F248-11E8-B48F-1D18A9856A87
last_name: Tasciyan
orcid: 0000-0003-1671-393X
- first_name: Masa
full_name: Ivin, Masa
last_name: Ivin
- first_name: Franz
full_name: Kratochvill, Franz
last_name: Kratochvill
- first_name: Nina
full_name: Gratz, Nina
last_name: Gratz
- first_name: Lukas
full_name: Kenner, Lukas
last_name: Kenner
- first_name: Andreas
full_name: Villunger, Andreas
last_name: Villunger
- first_name: Michael K
full_name: Sixt, Michael K
id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87
last_name: Sixt
orcid: 0000-0002-6620-9179
- first_name: Pavel
full_name: Kovarik, Pavel
last_name: Kovarik
citation:
ama: Ebner F, Sedlyarov V, Tasciyan S, et al. The RNA-binding protein tristetraprolin
schedules apoptosis of pathogen-engaged neutrophils during bacterial infection.
The Journal of Clinical Investigation. 2017;127(6):2051-2065. doi:10.1172/JCI80631
apa: Ebner, F., Sedlyarov, V., Tasciyan, S., Ivin, M., Kratochvill, F., Gratz, N.,
… Kovarik, P. (2017). The RNA-binding protein tristetraprolin schedules apoptosis
of pathogen-engaged neutrophils during bacterial infection. The Journal of
Clinical Investigation. American Society for Clinical Investigation. https://doi.org/10.1172/JCI80631
chicago: Ebner, Florian, Vitaly Sedlyarov, Saren Tasciyan, Masa Ivin, Franz Kratochvill,
Nina Gratz, Lukas Kenner, Andreas Villunger, Michael K Sixt, and Pavel Kovarik.
“The RNA-Binding Protein Tristetraprolin Schedules Apoptosis of Pathogen-Engaged
Neutrophils during Bacterial Infection.” The Journal of Clinical Investigation.
American Society for Clinical Investigation, 2017. https://doi.org/10.1172/JCI80631.
ieee: F. Ebner et al., “The RNA-binding protein tristetraprolin schedules
apoptosis of pathogen-engaged neutrophils during bacterial infection,” The
Journal of Clinical Investigation, vol. 127, no. 6. American Society for Clinical
Investigation, pp. 2051–2065, 2017.
ista: Ebner F, Sedlyarov V, Tasciyan S, Ivin M, Kratochvill F, Gratz N, Kenner L,
Villunger A, Sixt MK, Kovarik P. 2017. The RNA-binding protein tristetraprolin
schedules apoptosis of pathogen-engaged neutrophils during bacterial infection.
The Journal of Clinical Investigation. 127(6), 2051–2065.
mla: Ebner, Florian, et al. “The RNA-Binding Protein Tristetraprolin Schedules Apoptosis
of Pathogen-Engaged Neutrophils during Bacterial Infection.” The Journal of
Clinical Investigation, vol. 127, no. 6, American Society for Clinical Investigation,
2017, pp. 2051–65, doi:10.1172/JCI80631.
short: F. Ebner, V. Sedlyarov, S. Tasciyan, M. Ivin, F. Kratochvill, N. Gratz, L.
Kenner, A. Villunger, M.K. Sixt, P. Kovarik, The Journal of Clinical Investigation
127 (2017) 2051–2065.
date_created: 2018-12-11T11:47:53Z
date_published: 2017-06-01T00:00:00Z
date_updated: 2024-03-25T23:30:12Z
day: '01'
department:
- _id: MiSi
doi: 10.1172/JCI80631
external_id:
pmid:
- '28504646'
intvolume: ' 127'
issue: '6'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5451238/
month: '06'
oa: 1
oa_version: Submitted Version
page: 2051 - 2065
pmid: 1
project:
- _id: 25985A36-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: T00817-B21
name: The biochemical basis of PAR polarization
- _id: 25E9AF9E-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: P27201-B22
name: Revealing the mechanisms underlying drug interactions
publication: The Journal of Clinical Investigation
publication_identifier:
issn:
- '00219738'
publication_status: published
publisher: American Society for Clinical Investigation
publist_id: '7038'
quality_controlled: '1'
related_material:
record:
- id: '12401'
relation: dissertation_contains
status: public
scopus_import: 1
status: public
title: The RNA-binding protein tristetraprolin schedules apoptosis of pathogen-engaged
neutrophils during bacterial infection
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 127
year: '2017'
...
---
_id: '960'
abstract:
- lang: eng
text: The human cerebral cortex is the seat of our cognitive abilities and composed
of an extraordinary number of neurons, organized in six distinct layers. The establishment
of specific morphological and physiological features in individual neurons needs
to be regulated with high precision. Impairments in the sequential developmental
programs instructing corticogenesis lead to alterations in the cortical cytoarchitecture
which is thought to represent the major underlying cause for several neurological
disorders including neurodevelopmental and psychiatric diseases. In this review
we discuss the role of cell polarity at sequential stages during cortex development.
We first provide an overview of morphological cell polarity features in cortical
neural stem cells and newly-born postmitotic neurons. We then synthesize a conceptual
molecular and biochemical framework how cell polarity is established at the cellular
level through a break in symmetry in nascent cortical projection neurons. Lastly
we provide a perspective how the molecular mechanisms applying to single cells
could be probed and integrated in an in vivo and tissue-wide context.
article_number: '176'
article_processing_charge: Yes
author:
- first_name: Andi H
full_name: Hansen, Andi H
id: 38853E16-F248-11E8-B48F-1D18A9856A87
last_name: Hansen
- first_name: Christian F
full_name: Düllberg, Christian F
id: 459064DC-F248-11E8-B48F-1D18A9856A87
last_name: Düllberg
orcid: 0000-0001-6335-9748
- first_name: Christine
full_name: Mieck, Christine
id: 34CAE85C-F248-11E8-B48F-1D18A9856A87
last_name: Mieck
orcid: 0000-0003-1919-7416
- first_name: Martin
full_name: Loose, Martin
id: 462D4284-F248-11E8-B48F-1D18A9856A87
last_name: Loose
orcid: 0000-0001-7309-9724
- 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, Düllberg CF, Mieck C, Loose M, Hippenmeyer S. Cell polarity in cerebral
cortex development - cellular architecture shaped by biochemical networks. Frontiers
in Cellular Neuroscience. 2017;11. doi:10.3389/fncel.2017.00176
apa: Hansen, A. H., Düllberg, C. F., Mieck, C., Loose, M., & Hippenmeyer, S.
(2017). Cell polarity in cerebral cortex development - cellular architecture shaped
by biochemical networks. Frontiers in Cellular Neuroscience. Frontiers
Research Foundation. https://doi.org/10.3389/fncel.2017.00176
chicago: Hansen, Andi H, Christian F Düllberg, Christine Mieck, Martin Loose, and
Simon Hippenmeyer. “Cell Polarity in Cerebral Cortex Development - Cellular Architecture
Shaped by Biochemical Networks.” Frontiers in Cellular Neuroscience. Frontiers
Research Foundation, 2017. https://doi.org/10.3389/fncel.2017.00176.
ieee: A. H. Hansen, C. F. Düllberg, C. Mieck, M. Loose, and S. Hippenmeyer, “Cell
polarity in cerebral cortex development - cellular architecture shaped by biochemical
networks,” Frontiers in Cellular Neuroscience, vol. 11. Frontiers Research
Foundation, 2017.
ista: Hansen AH, Düllberg CF, Mieck C, Loose M, Hippenmeyer S. 2017. Cell polarity
in cerebral cortex development - cellular architecture shaped by biochemical networks.
Frontiers in Cellular Neuroscience. 11, 176.
mla: Hansen, Andi H., et al. “Cell Polarity in Cerebral Cortex Development - Cellular
Architecture Shaped by Biochemical Networks.” Frontiers in Cellular Neuroscience,
vol. 11, 176, Frontiers Research Foundation, 2017, doi:10.3389/fncel.2017.00176.
short: A.H. Hansen, C.F. Düllberg, C. Mieck, M. Loose, S. Hippenmeyer, Frontiers
in Cellular Neuroscience 11 (2017).
date_created: 2018-12-11T11:49:25Z
date_published: 2017-06-28T00:00:00Z
date_updated: 2024-03-25T23:30:23Z
day: '28'
ddc:
- '570'
department:
- _id: SiHi
- _id: MaLo
doi: 10.3389/fncel.2017.00176
ec_funded: 1
external_id:
isi:
- '000404486700001'
file:
- access_level: open_access
checksum: dc1f5a475b918d09a0f9f587400b1626
content_type: application/pdf
creator: system
date_created: 2018-12-12T10:09:40Z
date_updated: 2020-07-14T12:48:16Z
file_id: '4764'
file_name: IST-2017-830-v1+1_2017_Hansen_CellPolarity.pdf
file_size: 2153858
relation: main_file
file_date_updated: 2020-07-14T12:48:16Z
has_accepted_license: '1'
intvolume: ' 11'
isi: 1
language:
- iso: eng
month: '06'
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: 25D7962E-B435-11E9-9278-68D0E5697425
grant_number: RGP0053/2014
name: Quantitative Structure-Function Analysis of Cerebral Cortex Assembly at Clonal
Level
- _id: 25681D80-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '291734'
name: International IST Postdoc Fellowship Programme
- _id: 25985A36-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: T00817-B21
name: The biochemical basis of PAR polarization
publication: Frontiers in Cellular Neuroscience
publication_identifier:
issn:
- '16625102'
publication_status: published
publisher: Frontiers Research Foundation
publist_id: '6445'
pubrep_id: '830'
quality_controlled: '1'
related_material:
record:
- id: '9962'
relation: dissertation_contains
status: public
scopus_import: '1'
status: public
title: Cell polarity in cerebral cortex development - cellular architecture shaped
by biochemical networks
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: 11
year: '2017'
...