PTEN and the PTEN-like phosphatase CnrN have both distinct and overlapping roles in a Dictyostelium chemorepulsion pathway

TL;DR

This study shows how two similar proteins, PTEN and CnrN, work together in Dictyostelium cells to help them move away from a harmful chemical signal.

Contribution

The study reveals distinct and overlapping roles of PTEN and CnrN in chemorepulsion, a poorly understood process in eukaryotic cells.

Findings

PTEN and CnrN both inhibit Ras activation and reduce PI(3,4,5)P3 levels in response to the chemorepellent AprA.

AprA requires both PTEN and CnrN to increase PI(4,5)P2 levels and alter cell morphology.

PTEN uniquely decreases PI(4,5)P2 levels and induces cell roundness in response to AprA.

Abstract

Little is known about eukaryotic chemorepulsion. The enzymes phosphatase and tensin homolog (PTEN) and CnrN dephosphorylate phosphatidylinositol 3,4,5-trisphosphate [PI(3,4,5)P3] to phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2]. Dictyostelium discoideum cells require both PTEN and CnrN to induce chemorepulsion of cells away from the secreted chemorepellent protein AprA. How D. discoideum cells utilize two proteins with redundant phosphatase activities in response to AprA is unclear. Here, we show that D. discoideum cells require both PTEN and CnrN to locally inhibit Ras activation, decrease basal levels of PI(3,4,5)P3 and increase basal numbers of macropinosomes, and AprA prevents this increase. AprA requires both PTEN and CnrN to increase PI(4,5)P2 levels, decrease PI(3,4,5)P3 levels, inhibit proliferation, decrease myosin II phosphorylation and increase filopod sizes. PTEN, but not CnrN, decreases basal levels of PI(4,5)P2, and AprA requires PTEN, but not CnrN, to induce cell roundness. Together, our results suggest that CnrN and PTEN play unique roles in AprA-induced chemorepulsion.

Summary: Dictyostelium discoideum cells use two proteins with similar phosphatase functions, each playing unique roles, possibly in dephosphorylating PI(3,4,5)P3 in different membrane areas, to mediate movement away from a chemorepellent.

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