Phosphodiesterase PdeD, dynacortin, and a Kelch repeat-containing protein are direct GSK3 substrates in Dictyostelium that contribute to chemotaxis towards cAMP

The migration of cells according to a diffusible chemical signal in their environment is called chemotaxis, and the slime mould Dictyostelium discoideum is widely used for the study of eukaryotic chemotaxis. Dictyostelium must sense chemicals, such as cAMP, secreted during starvation to move towards the sources of the signal. Previous work demonstrated that the gskA gene encodes the Dictyostelium homologue of glycogen synthase kinase 3 (GSK3), a highly conserved serine/threonine kinase, which plays a major role in the regulation of Dictyostelium chemotaxis. Cells lacking the GskA substrates Daydreamer and GflB exhibited chemotaxis defects less severe than those exhibited by gskA- (GskA null) cells, suggesting that additional GskA substrates might be involved in chemotaxis. Using phosphoproteomics, the authors identify the GskA substrates PdeD, dynacortin and SogA and characterise the phenotypes of their respective null cells in response to the chemoattractant cAMP. All three chemotaxis phenotypes are defective, and in addition, we determine that carboxylesterase D2 is a common downstream effector of GskA, its direct substrates PdeD, GflB and the kinases GlkA and YakA, and that it also contributes to cell migration. The findings identify new GskA substrates in cAMP signalling and break down the essential role of GskA in myosin II regulation.

Authors: Baumgardner K, Lin C, Firtel RA, Lacal J, ; Full Source: Environmental Microbiology. 2018 May;20(5):1888-1903. doi: 10.1111/1462-2920.14126.