Molecular determinants of αVβ5 localization in flat clathrin lattices - role of αVβ5 in cell adhesion and proliferation.
Flat clathrin lattice
Focal adhesion
Integrin
Proliferation
Vitronectin
Journal
Journal of cell science
ISSN: 1477-9137
Titre abrégé: J Cell Sci
Pays: England
ID NLM: 0052457
Informations de publication
Date de publication:
01 06 2022
01 06 2022
Historique:
received:
13
10
2021
accepted:
20
04
2022
pubmed:
10
5
2022
medline:
9
6
2022
entrez:
9
5
2022
Statut:
ppublish
Résumé
The vitronectin receptor integrin αVβ5 can reside in two distinct adhesion structures - focal adhesions (FAs) and flat clathrin lattices (FCLs). Here, we investigate the mechanism that regulates the subcellular distribution of β5 in keratinocytes and show that β5 has approximately 7- and 5-fold higher affinity for the clathrin adaptors ARH (also known as LDLRAP1) and Numb, respectively, than for the talin 1 (TLN1); all proteins that bind to the membrane-proximal NPxY motif of the β5 cytoplasmic domain. Using mass spectrometry, we identified β5 interactors, including the Rho GEFs p115Rho-GEF and GEF-H1 (also known as ARHGEF1 and ARHGEF2, respectively), and the serine protein kinase MARK2, depletion of which diminishes the clustering of β5 in FCLs. Replacement of two serine residues (S759 and S762) in the β5 cytoplasmic domain with phospho-mimetic glutamate residues causes a shift in the localization of β5 from FAs into FCLs without affecting the interactions with MARK2, p115Rho-GEF or GEF-H1. Instead, we demonstrate that changes in the actomyosin-based cellular contractility by ectopic expression of activated Rho or disruption of microtubules regulates β5 localization. Finally, we present evidence that β5 in either FAs or FCLs functions to promote adhesion to vitronectin, cell spreading, and proliferation.
Identifiants
pubmed: 35532004
pii: 275569
doi: 10.1242/jcs.259465
pmc: PMC9234671
pii:
doi:
Substances chimiques
Clathrin
0
Receptors, Vitronectin
0
Serine
452VLY9402
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Nederlandse Organisatie voor Wetenschappelijk Onderzoek
ID : 824.14.010
Organisme : Dutch Cancer Society
ID : 12143
Organisme : Dutch NWO X-omics Initiative
Organisme : Alexander von Humboldt Foundation
Organisme : Netherlands Cancer Institute
Informations de copyright
© 2022. Published by The Company of Biologists Ltd.
Déclaration de conflit d'intérêts
Competing interests The authors declare no competing or financial interests.
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