PT  - JOURNAL ARTICLE
AU  - Shashi Kumar Suman
AU  - Csaba Daday
AU  - Teresa Ferraro
AU  - Thanh Vuong-Brender
AU  - Saurabh Tak
AU  - Sophie Quintin
AU  - François Robin
AU  - Frauke Gräter
AU  - Michel Labouesse
TI  - The <em>C. elegans</em> plectin homologue VAB-10 acts as a hemidesmosome mechanosensor
AID  - 10.1101/681072
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 681072
4099  - http://biorxiv.org/content/early/2019/06/26/681072.short
4100  - http://biorxiv.org/content/early/2019/06/26/681072.full
AB  - Mechanical forces control many cellular processes by eliciting mechanotransduction upon changes in tension (mechanosensing). Whereas mechanosensors acting at focal adhesion and adherens junction are known, they remain undefined for hemidesmosomes. Here, we focus on the C. elegans plectin homolog VAB-10A, the only evolutionary conserved hemidesmosome component. In C. elegans, muscles contractions induce a mechanotransduction pathway in the epidermis involving hemidesmosomes. We used CRISPR to precisely remove spectrin repeats (SR) or a partially hidden Src-homology-3 (SH3) domain within the VAB-10 plakin domain. Deleting the SH3 domain in combination with mutations affecting mechanotransduction, or just 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. Interestingly, Molecular Dynamics simulations confirmed that forces acting on VAB-10 relieve the inhibition of the central SH3 domain by the adjacent spectrin repeats. Collectively, our data strongly argue that we identified a hemidesmosome mechanosensor and that the SH3 domain, together with its shielding spectrin repeat, play a key role in mechanosensing.