RT Journal Article
SR Electronic
T1 Stress fiber strain recognition by the LIM protein testin is cryptic and mediated by RhoA
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.01.21.427693
DO 10.1101/2021.01.21.427693
A1 Sala, Stefano
A1 Oakes, Patrick W.
YR 2021
UL http://biorxiv.org/content/early/2021/03/31/2021.01.21.427693.abstract
AB The actin cytoskeleton is a key regulator of mechanical processes in cells. The family of LIM domain proteins have recently emerged as important mechanoresponsive cytoskeletal elements capable of sensing strain in the actin cytoskeleton. The mechanisms regulating this mechanosensitive behavior, however, remain poorly understood. Here we show that the LIM domain protein testin is peculiar in that despite the full-length protein primarily appearing diffuse in the cytoplasm, the C-terminal LIM domains alone recognize focal adhesions and strained actin while the N-terminal domains alone recognize stress fibers. Phosphorylation mutations in the dimerization regions of testin, however, reveal its mechanosensitivity and cause it to relocate to focal adhesions and sites of strain in the actin cytoskeleton. Finally, we demonstrate activated RhoA causes testin to adorn stress fibers and become mechanosensitive. Together, our data show that testin’s mechanoresponse is regulated in cells and provide new insights into LIM domain protein recognition of the actin cytoskeleton mechanical state.Competing Interest StatementThe authors have declared no competing interest.CAconstitutively activeCRcysteine richDNdominant-negativeFAfocal adhesionFHLfour- and-a-half LIMFLfull-lengthHFFhuman foreskin fibroblastLDPLIM domain proteinLIMLin-11, Isl-1, Mec-3MEFmouse embryonic fibroblastPETPrickle, Espinas, TestinSFstress fiberSFSSstress fiber strain site