LFA-1 signals to promote actin polymerization and upstream migration in T cells.
Actin
Integrins
Migration
Shear flow
Signaling
T cell
Journal
Journal of cell science
ISSN: 1477-9137
Titre abrégé: J Cell Sci
Pays: England
ID NLM: 0052457
Informations de publication
Date de publication:
09 09 2020
09 09 2020
Historique:
received:
29
04
2020
accepted:
28
07
2020
entrez:
10
9
2020
pubmed:
11
9
2020
medline:
22
6
2021
Statut:
epublish
Résumé
T cell entry into inflamed tissue requires firm adhesion, cell spreading, and migration along and through the endothelial wall. These events require the T cell integrins LFA-1 and VLA-4 and their endothelial ligands ICAM-1 and VCAM-1, respectively. T cells migrate against the direction of shear flow on ICAM-1 and with the direction of shear flow on VCAM-1, suggesting that these two ligands trigger distinct cellular responses. However, the contribution of specific signaling events downstream of LFA-1 and VLA-4 has not been explored. Using primary mouse T cells, we found that engagement of LFA-1, but not VLA-4, induces cell shape changes associated with rapid 2D migration. Moreover, LFA-1 ligation results in activation of the phosphoinositide 3-kinase (PI3K) and ERK pathways, and phosphorylation of multiple kinases and adaptor proteins, whereas VLA-4 ligation triggers only a subset of these signaling events. Importantly, T cells lacking Crk adaptor proteins, key LFA-1 signaling intermediates, or the ubiquitin ligase cCbl (also known as CBL), failed to migrate against the direction of shear flow on ICAM-1. These studies identify novel signaling differences downstream of LFA-1 and VLA-4 that drive T cell migratory behavior.This article has an associated First Person interview with the first author of the paper.
Identifiants
pubmed: 32907931
pii: jcs.248328
doi: 10.1242/jcs.248328
pmc: PMC7502589
pii:
doi:
Substances chimiques
Actins
0
Lymphocyte Function-Associated Antigen-1
0
Vascular Cell Adhesion Molecule-1
0
Intercellular Adhesion Molecule-1
126547-89-5
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIGMS NIH HHS
ID : R01 GM104867
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM123019
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL128551
Pays : United States
Organisme : NCI NIH HHS
ID : T32 CA009140
Pays : United States
Informations de copyright
© 2020. Published by The Company of Biologists Ltd.
Déclaration de conflit d'intérêts
Competing interestsThe authors declare no competing or financial interests.
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