Beyond cargo clearance: p62 coordinates cAMP signalling and autophagy to drive cell fate decisions in Dictyostelium discoideum

p62 is a multi-domain selective autophagy receptor and signaling scaffold conserved across eukaryotes. However, its evolutionary roots and functional significance in early-diverging eukaryotes like Dictyostelium have remained unexplored. In our recent study, we characterized p62 in the social amoeba Dictyostelium discoideum. Loss of p62 significantly delayed the starvation induced development and led to the formation of smaller multicellular structures. Altered p62 levels also disrupted autophagy flux and cell fate commitment in Dictyostelium cells. Treatment of p62 knockout (p62−) cells with pulses of exogenous cyclic AMP (cAMP) partially rescued developmental defects, suggesting a potential role for p62 in sustaining intracellular cAMP levels necessary for development. Taken together, p62 emerges as an evolutionarily conserved coordinator of nutrient sensing, second messenger signaling, and autophagy that promotes multicellular development in Dictyostelium.