| Journal Title /掲載ジャーナル名 |
PLoS Genetics |
| Publication Year and Month /掲載年月 |
October, 2022 |
| Paper Title /論文タイトル |
Inka2,a novel Pak4 inhibitor,regulates actin dynamics in neuronal development |
| DOI /論文DOI |
10.1371/journal.pgen.1010438 |
| Author of Waseda University /本学の著者 |
SAKAKIBARA, Shinichi(Professor, Faculty of Human Sciences, School of Human Sciences):Corresponding Author |
| Related Websites /関連Web |
– |
| Abstract /抄録 |
The actin filament is a fundamental part of the cytoskeleton defining cell morphology and regulating various physiological processes, including filopodia formation and dendritic spinogenesis of neurons. Serine/threonine-protein kinase Pak4, an essential effector, links Rho GTPases to control actin polymerization. Previously, we identified the Inka2 gene, a novel mammalian protein exhibiting sequence similarity to Inka1, which serves as a possible inhibitor for Pak4. Although Inka2 is dominantly expressed in the nervous system and involved in focal-adhesion dynamics, its molecular role remains unclear. Here, we found that Inka2-iBox directly binds to Pak4 catalytic domain to suppress actin polymerization. Inka2 promoted actin depolymerization and inhibited the formation of cellular protrusion caused by Pak4 activation. We further generated the conditional knockout mice of the Inka2 gene. The beta-galactosidase reporter indicated the preferential Inka2 expression in the dorsal forebrain neurons. Cortical pyramidal neurons of Inka2-/- mice exhibited decreased density and aberrant morphology of dendritic spines with marked activation/phosphorylation of downstream molecules of Pak4 signal cascade, including LIMK and Cofilin. These results uncovered the unexpected function of endogenous Pak4 inhibitor in neurons. Unlike Inka1, Inka2 is a critical mediator for actin reorganization required for dendritic spine development. |
