Regulation for Phosphatidylinositol Lipids Signaling System by Talin

Abstract

Cellular motility is a basic function underlying various important physiological phenomena. Actomyosin system generally works as an internal force generator, and external stimulations received via receptor-mediated signaling systems and an adhesive system modulate the motility. The force-generating, signaling and adhesive systems work in cooperation to make a united anterior-posterior polarity, which ensures an effective and adaptive cell migration. The actin polymerization is induced by PI(3,4,5)P3-enriched domains on the cell membrane, which arise from a chemotactic signaling system including PI(3,4,5)P3-producing PI3-kinase and egrading PTEN in a self-organized manner. However, how the adhesive system is correlated to the PtdIns system is unknown, which should to be an essential mechanism in regulating a migration mode dependently on whether the cells move solitarily or collectively. We examined effects of loss-of-function of focal adhesion on the PtdIns dynamics in single-celled amoebae and multicellular structures of Dictyostelium discoideum. amoebae of a mutant lacking a component of focal adhesion, talin, by disruptions of talA and talB, did not adhere to the substratum and exhibited an enhancement of PI(3,4,5)P3 domains traveling on the cell membrane. Due to the conditional up-regulation of PI(3,4,5)P3 production, a response to chemoattractant stimulation was abrogated. Both the PI(3,4,5)P3 dynamics in resting and stimulated cells was recovered by a treatment with PI3-kinase inhibitor, indicating talin suppresses PI3-kinase activity. A single disruption of talB, not talA, reconstructed the abnormal PI(3,4,5)P3 dynamics, suggesting talB is more responsible. The talB lacking cells failed to move collectively in the multicellular structures. Therefore, talin may be coupling the adhesion and PtdIns signaling systems via PI3-kinase, and multicellular collective motion is possibly mediated through the coupling by talinB.