A Dictyostelium Secreted Factor Requires a PTEN-Like Phosphatase to Slow Proliferation and Induce Chemorepulsion

Abstract

In Dictyostelium discoideum, AprA and CfaD are secreted proteins that inhibit cell proliferation. We found that the proliferation of cells lacking CnrN, a phosphatase and tensin homolog (PTEN)-like phosphatase, is not inhibited by exogenous AprA and is increased by exogenous CfaD. The expression of CnrN in cnrN¯ cells partially rescues these altered sensitivities, suggesting that CnrN is necessary for the ability of AprA and CfaD to inhibit proliferation. Cells lacking CnrN accumulate normal levels of AprA and CfaD. Like cells lacking AprA and CfaD, cnrN¯ cells proliferate faster and reach a higher maximum cell density than wild type cells, tend to be multinucleate, accumulate normal levels of mass and protein per nucleus, and form less viable spores. When cnrN¯ cells expressing myc-tagged CnrN are stimulated with a mixture of rAprA and rCfaD, levels of membrane-associated myc-CnrN increase. AprA also causes chemorepulsion of Dictyostelium cells, and CnrN is required for this process. Combined, these results suggest that CnrN functions in a signal transduction pathway downstream of AprA and CfaD mediating some, but not all, of the effects of AprA and CfaD.

Impaired neutrophil directional chemotactic accuracy in chronic periodontitis patients

“…Other studies (Henry et al 1984 ) employed the checkerboard assay described by Zigmond & Hirsch ( 1973 ). The use of the Insall chamber has recently expanded (Phillips & Gomer 2012 , Choi et al 2013 , Herlihy et al 2013a , b , Kaul et al 2013 ) and opened up new research questions, which informed the present study. Here, we report on speed, velocity and chemotactic accuracy.…”

An Autocrine Proliferation Repressor Regulates Dictyostelium discoideum Proliferation and Chemorepulsion Using the G Protein-Coupled Receptor GrlH

“…Both AprA and CfaD are necessary for proliferation inhibition, as recombinant AprA (rAprA) cannot rescue the cfaD¯ phenotype and recombinant CfaD (rCfaD) cannot rescue the aprA¯ phenotype ( 7 , 8 ). Several components of the AprA-induced and/or CfaD-induced proliferation inhibition signaling pathway have been identified, including the ROCO kinase QkgA, the p21-activated kinase (PAK) family member PakD, the PTEN-like phosphatase CnrN, and the tumor suppressor RblA ( 9 , 10 , 11 , 13 , 18 ). Additionally, AprA functions to chemorepel D. discoideum cells, causing cells to move in a biased direction away from a source of AprA ( 12 ).…”

“…Additionally, AprA functions to chemorepel D. discoideum cells, causing cells to move in a biased direction away from a source of AprA ( 12 ). QkgA, PakD, CnrN, and RblA are also involved in the AprA-induced-chemorepulsion signaling pathway ( 9 – 13 , 18 ). Both AprA inhibition of proliferation and AprA induction of chemorepulsion require the G proteins Gβ and Gα subunit Gα8, and the binding of AprA to cell membrane is inhibited by GTPγS, suggesting that AprA functions through binding to a G protein-coupled receptor (GPCR) ( 8 , 12 ).…”

Protease activated-receptor 2 is necessary for neutrophil chemorepulsion induced by trypsin, tryptase, or dipeptidyl peptidase IV

“…The chemorepellent AprA increased the directness of Dictyostelium cells, while DPPIV and the PAR2 agonists induced chemorepulsion without increasing directness. This suggests a difference in the chemorepulsion mechanisms used by AprA compared to the DPPIV and PAR2 agonists.…”