Deletion of Dictyostelium discoideum Sir2A impairs cell proliferation and inhibits autophagy

Sirtuins are a family of deacetylases (Class III histone deacetylases) with evolutionarily conserved functions in cellular metabolism and chromatin regulation. Out of the seven human Sirtuins, the function of Sirt2 is the least understood. The purpose of the present study was to investigate the role of Sir2A, a homolog of human Sirt2 in Dictyostelium discoideum (Dd), a lower eukaryote. We created both overexpressing and deletion strains of Ddsir2A to analyse its functions. We observed sir2A mRNA expression throughout development and the transcript was present in the prespore/spore region of multicellular structures developed. They show a preference towards prestalk/stalk pathway when co-developed with wild-type cells during chimera formation. Deletion strain showed a multi-tipped phenotype, decrease in cell proliferation and inhibition of autophagy. In conclusion, our results show low cAMP levels, reduced cell-adhesion, weak cell migration and impaired autophagy to be responsible for the phenotype shown by the null cells. This study provides new insights into the functions of Ddsir2A.