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

Ligand Binding to the Collagen VI Receptor Triggers a Talin-to-RhoA Switch that Regulates Receptor Endocytosis.
Dev Cell. 2020 May 18;53(4):418-430.e4
Authors: Bürgi J, Abrami L, Castanon I, Abriata LA, Kunz B, Yan SE, Lera M, Unger S, Superti-Furga A, Peraro MD, Gaitan MG, van der Goot FG
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.
PMID: 32428455 [PubMed - in process]

Source: Developmental Cell - May 17, 2020 Category: Cytology Authors: Bürgi J, Abrami L, Castanon I, Abriata LA, Kunz B, Yan SE, Lera M, Unger S, Superti-Furga A, Peraro MD, Gaitan MG, van der Goot FG Tags: Dev Cell Source Type: research