Dictyostelium discoideum Sir2D modulates cell-type specific gene expression and is involved in autophagy

Sirtuins (SIRTs) belong to class III histone deacetylases and require NAD⁺ for their activity. Their activity is associated with the nutritional status of the cell and they directly link cellular metabolic signalling to the state of protein post-translational modifications. Sirtuins play an important role in healthy aging, longevity and age-related diseases, as well as in cell survival mechanisms, such as autophagy. Here, we investigate the functions of Dictyostelium discoideum Sir2D which shows similarity to human SIRT1. This gene is expressed throughout growth and development. Overexpression of sir2D promotes cell proliferation and the corresponding fusion protein shows nuclear localization. To facilitate the study of the function of Sir2D, we created a sir2D knockout by gene disruption. This mutant exhibits inhibited cell proliferation and developmental defects, including smaller aggregates and multi-tipped structures. When developed as chimeras with wild-type cells, the sir2D^- cells show a reduced ability to form spores. Prespore and prestalk differentiation was also impaired in the mutant strain. Sir2D regulates the expression of several autophagic genes (Atgs) and the sir2D deficient strain shows reduced autophagic flux. In conclusion, Sir2D plays a role in cell differentiation, modulates the expression of both prespore and prestalk genes and participates in the process of autophagy.