Molecular determinants of αVβ5 localization in flat clathrin lattices - role of αVβ5 in cell adhesion and proliferation.

Autor:	Zuidema A; Division of Cell Biology I, The Netherlands Cancer Institute, Plesmanlaan 121, Amsterdam 1066 CX, The Netherlands., Wang W; Division of Cell Biology I, The Netherlands Cancer Institute, Plesmanlaan 121, Amsterdam 1066 CX, The Netherlands., Kreft M; Division of Cell Biology I, The Netherlands Cancer Institute, Plesmanlaan 121, Amsterdam 1066 CX, The Netherlands., Bleijerveld OB; Proteomics Facility, The Netherlands Cancer Institute, Amsterdam 1066 CX, The Netherlands., Hoekman L; Proteomics Facility, The Netherlands Cancer Institute, Amsterdam 1066 CX, The Netherlands., Aretz J; Department of Molecular Medicine, Max Planck Institute of Biochemistry, Am Klopfespitz 18, 82152 Martinsried, Germany., Böttcher RT; Department of Molecular Medicine, Max Planck Institute of Biochemistry, Am Klopfespitz 18, 82152 Martinsried, Germany., Fässler R; Department of Molecular Medicine, Max Planck Institute of Biochemistry, Am Klopfespitz 18, 82152 Martinsried, Germany., Sonnenberg A; Division of Cell Biology I, The Netherlands Cancer Institute, Plesmanlaan 121, Amsterdam 1066 CX, The Netherlands.
Jazyk:	angličtina
Zdroj:	Journal of cell science [J Cell Sci] 2022 Jun 01; Vol. 135 (11). Date of Electronic Publication: 2022 Jun 06.
DOI:	10.1242/jcs.259465
Abstrakt:	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. Competing Interests: Competing interests The authors declare no competing or financial interests. (© 2022. Published by The Company of Biologists Ltd.)
Databáze:	MEDLINE
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