{Reference Type}: Journal Article
{Title}: Caskin2 is a novel talin- and Abi1-binding protein that promotes cell motility.
{Author}: Wang W;Atherton P;Kreft M;Te Molder L;van der Poel S;Hoekman L;Celie P;Joosten RP;Fässler R;Perrakis A;Sonnenberg A;
{Journal}: J Cell Sci
{Volume}: 137
{Issue}: 9
{Year}: 2024 May 1
{Factor}: 5.235
{DOI}: 10.1242/jcs.262116
{Abstract}: Talin (herein referring collectively to talin 1 and 2) couples the actomyosin cytoskeleton to integrins and transmits tension to the extracellular matrix. Talin also interacts with numerous additional proteins capable of modulating the actin-integrin linkage and thus downstream mechanosignaling cascades. Here, we demonstrate that the scaffold protein Caskin2 interacts directly with the R8 domain of talin through its C-terminal LD motif. Caskin2 also associates with the WAVE regulatory complex to promote cell migration in an Abi1-dependent manner. Furthermore, we demonstrate that the Caskin2-Abi1 interaction is regulated by growth factor-induced phosphorylation of Caskin2 on serine 878. In MCF7 and UACC893 cells, which contain an amplification of CASKIN2, Caskin2 localizes in plasma membrane-associated plaques and around focal adhesions in cortical microtubule stabilization complexes. Taken together, our results identify Caskin2 as a novel talin-binding protein that might not only connect integrin-mediated adhesion to actin polymerization but could also play a role in crosstalk between integrins and microtubules.