Ligand Binding to the Collagen VI Receptor Triggers a Talin-to-RhoA Switch that Regulates Receptor Endocytosis.

Details

Serval ID
serval:BIB_589E9F0B5581
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Ligand Binding to the Collagen VI Receptor Triggers a Talin-to-RhoA Switch that Regulates Receptor Endocytosis.
Journal
Developmental cell
Author(s)
Bürgi J., Abrami L., Castanon I., Abriata L.A., Kunz B., Yan S.E., Lera M., Unger S., Superti-Furga A., Peraro M.D., Gaitan M.G., van der Goot F.G.
ISSN
1878-1551 (Electronic)
ISSN-L
1534-5807
Publication state
Published
Issued date
18/05/2020
Peer-reviewed
Oui
Volume
53
Number
4
Pages
418-430.e4
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
Capillary morphogenesis gene 2 (CMG2/ANTXR2) is a cell surface receptor for both collagen VI and anthrax toxin. Biallelic loss-of-function mutations in CMG2 lead to a severe condition, hyaline fibromatosis syndrome (HFS). We have here dissected a network of dynamic interactions between CMG2 and various actin interactors and regulators, describing a different behavior from other extracellular matrix receptors. CMG2 binds talin, and thereby the actin cytoskeleton, only in its ligand-free state. Extracellular ligand binding leads to src-dependent talin release and recruitment of the actin cytoskeleton regulator RhoA and its effectors. These sequential interactions of CMG2 are necessary for the control of oriented cell division during fish development. Finally, we demonstrate that effective switching between talin and RhoA binding is required for the intracellular degradation of collagen VI in human fibroblasts, which explains why HFS mutations in the cytoskeleton-binding domain lead to dysregulation of extracellular matrix homeostasis.
Keywords
GAPO syndrome, MYL12A, RhoA, Src, actin cytoskeleton, anthrax toxin receptor, collagen 6, extracellular matrix, hyaline fibromatosis syndrome, integrin
Pubmed
Web of science
Create date
10/07/2020 13:34
Last modification date
31/07/2020 5:26
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