Prickle1 promotes focal adhesion disassembly in cooperation with CLASP-LL5β complex in migrating cells

Abstract

Prickle is known to be involved in planar cell polarity including convergent extension and cell migration; however, the detailed mechanism by which Prickle regulates cellular functions is not well understood. Here, we show that Prickle1 regulates front-rear polarization and migration of gastric cancer MKN1 cells. Prickle1 preferentially accumulated at the cell retraction site in close proximity to paxillin at focal adhesions (FAs). Prickle1 dynamics were associated with those of paxillin during FA disassembly. Furthermore, Prickle1 was required for FA disassembly. CLASP and LL5β have been reported to form a complex at cell edge and controls microtubule-dependent FA disassembly. Prickle1 was associated with CLASP and LL5β, and was required for the LL5β-dependent accumulation of CLASP at the cell edge. Knockdown of CLASP and LL5β suppressed Prickle1-dependent cell polarization and migration. Prickle1 localized to the membrane through its farnesyl moiety, and the membrane localization was necessary for Prickle1's ability to regulate migration, bind to CLASP and LL5β, and promote microtubule targeting of FAs. Taken together, these results suggest that Prickle1 promotes FA disassembly during the retraction processes of cell polarization and migration.