Membrane transport in Caenorhabditis elegans: an essential role for VPS34 at the nuclear membrane

Here we present a detailed genetic analysis of let‐512/vps34 that encodes the Caenorhabditis elegans homologue of the yeast phosphatidylinositol 3‐kinase Vps34p. LET‐512/VPS34 has essential functions and is ubiquitously expressed in all tissues and developmental stages. It accumulates at a perinuclear region, and mutations in let‐512/vps34 result in an expansion of the outer nuclear membrane as well as in a mislocalization and subsequent complete lack of expression of LRP‐1, a C.elegans LDL receptor normally associated with the apical surface of hypodermal cells. Using a GFP::2xFYVE fusion protein we found that the phosphatidylinositol 3‐phosphate (PtdIns 3‐P) product of LET‐512/VPS34 is associated with a multitude of intracellular membranes and vesicles located at the periphery, including endocytic vesicles. We propose that LET‐512/VPS34 is required for membrane transport from the outer nuclear membrane towards the cell periphery. Thus, LET‐512/VPS34 may regulate the secretory pathway in a much broader range of compartments than was previously suggested for the yeast orthologue.