1. Naughty proteins are having fun in the secretory pathway: unusual roles for the exocysts and Vps34 complexes

MARIANA MELANI

Conferencia; Buenos Aires Conference on Autophagy,Vesicular Trafficking, Mechanisms and Disease; 2022

It is well accepted that inward, outward and intracellular vesicle trafficking pathways are interconnected and that the crosstalk among them is essential for the well-functioning and integrity of cellular compartments. This cross-communication is mediated by protein complexes that initially thought to be specific for one pathway, were later on identified to moonlight on others. That is the case, for example, for the exocyst and the PI3k complexes. The exocyst is a heteroctameric complex initially identified in yeast as required for polarized secretion at the budding tip. Molecularly, it works as a tethering factor to bring in close proximity a secretory vesicle and its target membrane, a critical step in the exocitic process that precedes SNARE activation and membrane fusion. The exocyst has been also shown to be play several roles in the autophagic process, both working as a scaffold platform that favours timely and localized activation of autophagic complex, and also in the closure of expanding autophagosomes. The PI3K complex also performs multiple roles in the autophagic and endocytic pathways, depending on the molecular partner that it associates with. The interaction of the core complex (formed by PI3K, Beclin 1 and VPS15) with Atg14, enhances its autophagic activity and autophagosome biogenesis, whereas its association with UVRAG stimulates endosomal and autophagosomal maturation. We have been studying regulated exocytosis using the salivary gland of Drosophila larvae as a genetic model system that can be easy manipulated and visualized. We have found previously unidentified functions for both the exocyst and the PI3K complex along the regulated exocytic pathway.