The G alpha subunit Gα8 inhibits proliferation, promotes adhesion and regulates cell differentiation

Abstract

Heterotrimeric G protein-mediated signal transduction plays a pivotal role in both vegetative and developmental stages in the eukaryote Dictyostelium discoideum. Here we describe novel functions of the G protein alpha subunit Gα8 during vegetative and development stages. Gα8 is expressed at low levels during vegetative growth. Loss of Gα8 promotes cell proliferation, whereas excess Gα8 expression dramatically inhibits growth and induces aberrant cytokinesis on substrates in a Gβ-dependent manner. Overexpression of Gα8 also leads to increased cell–cell cohesion and cell–substrate adhesion. We demonstrate that the increased cell–cell cohesion is mainly caused by induced CadA expression, and the induced cell– substrate adhesion is responsible for the cytokinesis defects. However, the expression of several putative constitutively active mutants of Gα8 does not augment the phenotypes caused by intact Gα8. Gα8 is strongly induced after starvation, and loss of Gα8 results in decreased expression of certain adhesion molecules including CsA and tgrC1. Interestingly, Gα8 is preferentially distributed in the upper and lower cup of the fruiting body. Lack of Gα8 decreases the expression of the specific marker of the anterior-like cells, suggesting that Gα8 is required for anterior-like cell differentiation.

Poly(ADP‐ribose) polymerase‐1 (PARP‐1) regulates developmental morphogenesis and chemotaxis in Dictyostelium discoideum

“…cAMP is one of the important signalling molecules in D. discoideum developmental morphogenesis, particularly during aggregation and late developmental stages [Mir et al., ]. Mutants that exhibit defects in aggregate formation have been reported to show altered expression of ACAA, CARA, PDSA and, REGA genes [Hirose et al., ; Wu and Janetopoulos, ; Garciandia and Suarez, ]. The effect of ADPRT1A KO on cAMP signalling was addressed by analysing the transcript levels of the aforementioned genes involved in cAMP signal transduction.…”

The Dictyostelium discoideum RACK1 orthologue has roles in growth and development

“…Gα2-null mutants do not aggregate and overexpression of wild-type Gα2 results in precocious activation of guanylyl cyclase by cAMP in vegetative cells [ 14 ]. Gα4 mediates responses to folic acid [ 15 ], and Gα8 inhibits proliferation, promotes adhesion and regulates cell differentiation [ 16 ]. D. discoideum cells lacking functional G protein β subunit are severely defective in phagocytosis, chemotaxis, aggregation, and development [ 17 , 12 - 21 ].…”