The lipid phosphatase-like protein PLPPR1 increases cell adhesion by modulating RhoA/Rac1 activity

Abstract

ABSTRACTPhospholipid Phosphatase-Related Protein Type 1 (PLPPR1) is a member of a family of lipid phosphatase related proteins, integral membrane proteins characterized by six transmembrane domains. PLPPR1 is enriched in the brain and recent data indicate potential pleiotropic functions in several different contexts. An inherent ability of PLPPR1 is to induce membrane protrusions, and we have previously reported that members within this family may act in concert. However, the mechanism by which PLPPR1 produces these actions is not yet understood. Here, we report that exogenous expression of PLPPR1 reduces cell motility and increases cell adhesion to the ECM substrate by altering cytoskeletal dynamics and modulating RhoA and Rac1 activity through association with RhoGDI. This signaling also allows overexpression of PLPPR1 to overcome the inhibitory activity of CSPGs and LPA on neurites. Together, these results establish a novel signaling pathway for the PLPPR1 protein.SUMMARYPLPPR1 increases cell adhesion and decreases cell motility by modulating RhoA and Rac1 activation through its association with RhoGDI.