VPS36 Activators

VPS36 (Vacuolar Protein Sorting-associated protein 36) is an integral component of the ESCRT-II complex (Endosomal Sorting Complex Required for Transport II), which is essential for the sorting of ubiquitinated membrane proteins into the internal vesicles of multivesicular bodies (MVBs). This process is critical for the downregulation of surface receptors and the trafficking of membrane proteins to the lysosome for degradation.The ESCRT-II complex, including VPS36, is involved in the recognition and sequestration of ubiquitinated proteins into the endosomal membrane. VPS36 specifically binds to ubiquitin via its GLUE (GRAM-like ubiquitin-binding in Eap45) domain, which is a unique feature distinguishing it from other ESCRT components. This interaction is pivotal for the sorting function of ESCRT-II.

VPS36 is also implicated in the late stages of cytokinesis and in the abscission process, where the final separation of the daughter cells occurs following mitosis. Additionally, it plays a role in the replication and pathogenesis of various viruses, as many viruses hijack the ESCRT machinery to bud from the host cell membrane.Dysfunction in the ESCRT machinery, including VPS36, can lead to diseases such as neurodegenerative disorders, cancer, and viral infections. The precise regulation of VPS36 and the ESCRT-II complex is therefore crucial for maintaining cellular homeostasis.