Cargando…

ARPC5 isoforms and their regulation by calcium-calmodulin-N-WASP drive distinct Arp2/3-dependent actin remodeling events in CD4 T cells

CD4 T cell activation induces nuclear and cytoplasmic actin polymerization via the Arp2/3 complex to activate cytokine expression and strengthen T cell receptor (TCR) signaling. Actin polymerization dynamics and filament morphology differ between nucleus and cytoplasm. However, it is unclear how the...

Descripción completa

Detalles Bibliográficos
Autores principales: Sadhu, Lopamudra, Tsopoulidis, Nikolaos, Hasanuzzaman, Md, Laketa, Vibor, Way, Michael, Fackler, Oliver T
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10171864/
https://www.ncbi.nlm.nih.gov/pubmed/37162507
http://dx.doi.org/10.7554/eLife.82450
_version_ 1785039512187961344
author Sadhu, Lopamudra
Tsopoulidis, Nikolaos
Hasanuzzaman, Md
Laketa, Vibor
Way, Michael
Fackler, Oliver T
author_facet Sadhu, Lopamudra
Tsopoulidis, Nikolaos
Hasanuzzaman, Md
Laketa, Vibor
Way, Michael
Fackler, Oliver T
author_sort Sadhu, Lopamudra
collection PubMed
description CD4 T cell activation induces nuclear and cytoplasmic actin polymerization via the Arp2/3 complex to activate cytokine expression and strengthen T cell receptor (TCR) signaling. Actin polymerization dynamics and filament morphology differ between nucleus and cytoplasm. However, it is unclear how the Arp2/3 complex mediates distinct nuclear and cytoplasmic actin polymerization in response to a common stimulus. In humans, the ARP3, ARPC1, and ARPC5 subunits of the Arp2/3 complex exist as two different isoforms, resulting in complexes with different properties. Here, we show that the Arp2/3 subunit isoforms ARPC5 and ARPC5L play a central role in coordinating distinct actin polymerization events in CD4 T cells. While ARPC5L is heterogeneously expressed in individual CD4 T cells, it specifically drives nuclear actin polymerization upon T cell activation. In contrast, ARPC5 is evenly expressed in CD4 T cell populations and is required for cytoplasmic actin dynamics. Interestingly, nuclear actin polymerization triggered by a different stimulus, DNA replication stress, specifically requires ARPC5 but not ARPC5L. TCR signaling but not DNA replication stress induces nuclear actin polymerization via nuclear calcium-calmodulin signaling and N-WASP. Diversity in the molecular properties and individual expression patterns of ARPC5 subunit isoforms thus tailors Arp2/3-mediated actin polymerization to different physiological stimuli.
format Online
Article
Text
id pubmed-10171864
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher eLife Sciences Publications, Ltd
record_format MEDLINE/PubMed
spelling pubmed-101718642023-05-11 ARPC5 isoforms and their regulation by calcium-calmodulin-N-WASP drive distinct Arp2/3-dependent actin remodeling events in CD4 T cells Sadhu, Lopamudra Tsopoulidis, Nikolaos Hasanuzzaman, Md Laketa, Vibor Way, Michael Fackler, Oliver T eLife Immunology and Inflammation CD4 T cell activation induces nuclear and cytoplasmic actin polymerization via the Arp2/3 complex to activate cytokine expression and strengthen T cell receptor (TCR) signaling. Actin polymerization dynamics and filament morphology differ between nucleus and cytoplasm. However, it is unclear how the Arp2/3 complex mediates distinct nuclear and cytoplasmic actin polymerization in response to a common stimulus. In humans, the ARP3, ARPC1, and ARPC5 subunits of the Arp2/3 complex exist as two different isoforms, resulting in complexes with different properties. Here, we show that the Arp2/3 subunit isoforms ARPC5 and ARPC5L play a central role in coordinating distinct actin polymerization events in CD4 T cells. While ARPC5L is heterogeneously expressed in individual CD4 T cells, it specifically drives nuclear actin polymerization upon T cell activation. In contrast, ARPC5 is evenly expressed in CD4 T cell populations and is required for cytoplasmic actin dynamics. Interestingly, nuclear actin polymerization triggered by a different stimulus, DNA replication stress, specifically requires ARPC5 but not ARPC5L. TCR signaling but not DNA replication stress induces nuclear actin polymerization via nuclear calcium-calmodulin signaling and N-WASP. Diversity in the molecular properties and individual expression patterns of ARPC5 subunit isoforms thus tailors Arp2/3-mediated actin polymerization to different physiological stimuli. eLife Sciences Publications, Ltd 2023-05-10 /pmc/articles/PMC10171864/ /pubmed/37162507 http://dx.doi.org/10.7554/eLife.82450 Text en © 2023, Sadhu et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Immunology and Inflammation
Sadhu, Lopamudra
Tsopoulidis, Nikolaos
Hasanuzzaman, Md
Laketa, Vibor
Way, Michael
Fackler, Oliver T
ARPC5 isoforms and their regulation by calcium-calmodulin-N-WASP drive distinct Arp2/3-dependent actin remodeling events in CD4 T cells
title ARPC5 isoforms and their regulation by calcium-calmodulin-N-WASP drive distinct Arp2/3-dependent actin remodeling events in CD4 T cells
title_full ARPC5 isoforms and their regulation by calcium-calmodulin-N-WASP drive distinct Arp2/3-dependent actin remodeling events in CD4 T cells
title_fullStr ARPC5 isoforms and their regulation by calcium-calmodulin-N-WASP drive distinct Arp2/3-dependent actin remodeling events in CD4 T cells
title_full_unstemmed ARPC5 isoforms and their regulation by calcium-calmodulin-N-WASP drive distinct Arp2/3-dependent actin remodeling events in CD4 T cells
title_short ARPC5 isoforms and their regulation by calcium-calmodulin-N-WASP drive distinct Arp2/3-dependent actin remodeling events in CD4 T cells
title_sort arpc5 isoforms and their regulation by calcium-calmodulin-n-wasp drive distinct arp2/3-dependent actin remodeling events in cd4 t cells
topic Immunology and Inflammation
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10171864/
https://www.ncbi.nlm.nih.gov/pubmed/37162507
http://dx.doi.org/10.7554/eLife.82450
work_keys_str_mv AT sadhulopamudra arpc5isoformsandtheirregulationbycalciumcalmodulinnwaspdrivedistinctarp23dependentactinremodelingeventsincd4tcells
AT tsopoulidisnikolaos arpc5isoformsandtheirregulationbycalciumcalmodulinnwaspdrivedistinctarp23dependentactinremodelingeventsincd4tcells
AT hasanuzzamanmd arpc5isoformsandtheirregulationbycalciumcalmodulinnwaspdrivedistinctarp23dependentactinremodelingeventsincd4tcells
AT laketavibor arpc5isoformsandtheirregulationbycalciumcalmodulinnwaspdrivedistinctarp23dependentactinremodelingeventsincd4tcells
AT waymichael arpc5isoformsandtheirregulationbycalciumcalmodulinnwaspdrivedistinctarp23dependentactinremodelingeventsincd4tcells
AT facklerolivert arpc5isoformsandtheirregulationbycalciumcalmodulinnwaspdrivedistinctarp23dependentactinremodelingeventsincd4tcells