PUBLICATION
Ligand Binding to the Collagen VI Receptor Triggers a Talin-to-RhoA Switch that Regulates Receptor Endocytosis
- Authors
- 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.
- ID
- ZDB-PUB-201215-22
- Date
- 2020
- Source
- Developmental Cell 53: 418-430.e4 (Journal)
- Registered Authors
- Castanon, Irinka
- Keywords
- GAPO syndrome, MYL12A, RhoA, Src, actin cytoskeleton, anthrax toxin receptor, collagen 6, extracellular matrix, hyaline fibromatosis syndrome, integrin
- MeSH Terms
-
- Animals
- Hyaline Fibromatosis Syndrome/genetics
- Hyaline Fibromatosis Syndrome/metabolism
- Hyaline Fibromatosis Syndrome/pathology*
- Female
- Receptors, Peptide/genetics
- Receptors, Peptide/metabolism*
- rhoA GTP-Binding Protein/genetics
- rhoA GTP-Binding Protein/metabolism*
- Talin/genetics
- Talin/metabolism*
- Collagen Type VI/metabolism*
- Ligands
- Humans
- Receptors, Collagen/genetics
- Receptors, Collagen/metabolism*
- Male
- Cytoskeleton/metabolism
- Endocytosis*
- Zebrafish
- Mutation
- PubMed
- 32428455 Full text @ Dev. Cell
Citation
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. (2020) Ligand Binding to the Collagen VI Receptor Triggers a Talin-to-RhoA Switch that Regulates Receptor Endocytosis. Developmental Cell. 53:418-430.e4.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping