Vps30

Vps30 is a gene in Saccharomyces cerevisiae that encodes the autophagy-related protein 6, the yeast homolog of Beclin1. It is a core component of the class III phosphatidylinositol 3-kinase (PI3K) complexes that regulate autophagy and vacuolar protein sorting, making it essential for membrane trafficking events that sustain cellular homeostasis under nutrient stress.

Vps30 forms part of two PI3K complexes with distinct roles. Complex I promotes autophagy and includes Vps34 (the catalytic PI3K), Vps15 (the regulatory subunit), Vps30/Atg6, and Atg14 as a subunit that confers autophagy specificity. Complex II governs endosomal trafficking and vacuolar sorting, comprising Vps34, Vps15, Vps30/Atg6, and Vps38 (the yeast UVRAG homolog). Both complexes generate phosphatidylinositol 3-phosphate (PI3P) to recruit downstream effectors at membranes, enabling autophagosome formation or endocytic cargo delivery.

Localization and function of Vps30 are coordinated at sites of autophagosome initiation, such as the pre-autophagosomal structure, where the PI3K complexes recruit effector proteins and promote membrane remodeling. Loss of Vps30 function leads to defective autophagy, abnormal vacuolar morphology, and impaired growth under nutrient-deprived conditions, reflecting its central role in autophagy and vacuolar trafficking.

Beclin1, the mammalian ortholog of Vps30, participates in similar PI3K complexes and autophagy regulation. Dysregulation of Beclin1 has been linked to various diseases, including cancer and neurodegenerative disorders, highlighting the conserved importance of Vps30/Beclin1 in cellular homeostasis. Overall, Vps30 is a key architect of autophagy initiation and vacuolar sorting through its integration into PI3K signaling complexes.