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

Phospholipid 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. SUMMARY PLPPR1 increases cell adhesion and decreases cell motility by modulating RhoA and Rac1 activation through its association with RhoGDI. * PLPPR : Phospholipid Phosphatase-Related Protein FA : Focal Adhesions CSPG : Chondroitin Sulfate Proteoglycan PLL : Poly-L-Lysine LPA : Lysophosphatidic acid LPP : Lipid Phosphate Phosphatase FAFBSA : Fatty Acid Free Bovine Serum Albumin MLC : myosin light chain II MYPT1 : myosin light chain phosphatase 1 ERM : Ezrin, Radixin and Moesin GSK : Glycogen Synthase Kinase GEF : Guanine Exchange Factor GAP : GTPase Activating Protein RhoGDI : Rho Guanine Nucleotide Dissociation Inhibitor IRM : Interference Reflection Microscopy TIRF : Total Internal Reflection Fluorescence STED : STimulated Emission Depletion FRAP : Fluorescence Recovery After Photobleaching ROCK : Rho-associated protein kinase CA : Constitutively Active DN : Dominant Negative FAK : Focal adhesion kinase GTP : Guanosine triphosphate GDP : Guanosine diphosphate WAVE : WASP-family verprolin-homologous protein).