Elena Morelli

Vesicular trafficking within cells is an important process for tissue development and homeostasis. We have isolated a loss of function mutant in the Drosophila homolog of snap29 gene, which encodes a ubiquitous SNARE protein (Snap29 hereafter) shown to be involved in membrane fusion. Lack of Snap29 functionality in Drosophila epithelial tissues correlates with defects of tissues architecture and development. Our findings support a role of Snap29 at key steps of membrane trafficking. In particular, we found that Snap29 is required for fusion of autophagosomes with lysosomes and that lack of Snap29 results in excess of secretion, suggesting that Snap29 might act negatively in regulation of vesicle fusion at the plasma membrane. Surprisingly, we found that both in Drosophila and mammalian cells Snap29 controls the attachment of mitotic fibers to kinetochores during mitosis. In mammalian cells, we show that lack of SNAP29 correlates with absence at kinetochores of ZWINT-1 and ZWILCH, a component of RZZ complex, with prometaphase delay and formation of daughter cells containing mininuclei. In vivo, we demonstrated that while autophagy defects are not the cause of the altered epithelial tissues architecture in snap29 mutants, defective mitotic phases are frequently found in snap29 mutant tissues suggesting that alterations of mitosis might be responsible for altered tissues phenotype. Our study contribute to shed light on the pathogenesis of CEDNIK, a human congenital syndrome caused by SNAP29 inactivation and we surmise that the function of SNAP29 at KT could be potentially relevant to development of aneuploidy in tumor-like masses.