RRC ID 59602
Author Suman SK, Daday C, Ferraro T, Vuong-Brender T, Tak S, Quintin S, Robin F, Gräter F, Labouesse M.
Title The plakin domain of C. elegans VAB-10/plectin acts as a hub in a mechanotransduction pathway to promote morphogenesis.
Journal Development
Abstract Mechanical forces can elicit a mechanotransduction response through junction-associated proteins. In contrast to the wealth of knowledge available for focal adhesions and adherens junctions, much less is known about mechanotransduction at hemidesmosomes. Here, we focus on the C. elegans plectin homolog VAB-10A, the only evolutionary conserved hemidesmosome component. In C. elegans, muscle contractions induce a mechanotransduction pathway in the epidermis through hemidesmosomes. We used CRISPR to precisely remove spectrin repeats (SRs) or a partially hidden Src homology 3 (SH3) domain within the VAB-10 plakin domain. Deleting the SH3 or SR8 domains in combination with mutations affecting mechanotransduction, or just the part of SR5 shielding the SH3 domain, induced embryonic elongation arrest because hemidesmosomes collapse. Notably, recruitment of GIT-1, the first mechanotransduction player, requires the SR5 domain and the hemidesmosome transmembrane receptor LET-805. Furthermore, molecular dynamics simulations confirmed that forces acting on VAB-10 could make the central SH3 domain, otherwise in contact with SR4, available for interaction. Collectively, our data strongly indicate that the plakin domain plays a central role in mechanotransduction and raise the possibility that VAB-10/plectin might act as a mechanosensor.
Volume 146(24)
Published 2019-12-13
DOI 10.1242/dev.183780
PII dev.183780
PMID 31784459
PMC PMC7375825
MeSH Animals Animals, Genetically Modified Caenorhabditis elegans / embryology Caenorhabditis elegans / genetics Caenorhabditis elegans Proteins / chemistry* Caenorhabditis elegans Proteins / genetics* Caenorhabditis elegans Proteins / physiology Embryo, Nonmammalian Epidermis / embryology Epidermis / metabolism Mechanotransduction, Cellular / genetics* Molecular Dynamics Simulation Morphogenesis / genetics* Protein Domains / genetics Protein Domains / physiology Time-Lapse Imaging
IF 5.763
Times Cited 1
C.elegans tm403 tm1962