Mechanistic roles of tyrosine phosphorylation in reversible amyloids, autoinhibition, and endosomal membrane association of ALIX

Abstract

ALIX is involved in a myriad of essential cellular processes, most notably acting within the ESCRT pathway to mediate events such as cytokinesis and exosome biogenesis. Regulation of ALIX has been suggested to involve intramolecular, autoinhibitory interactions between individual ALIX domains. Interaction with the tyrosine kinase Src results in inactivation and redistribution of ALIX from late endosomal membranes to the cytosol, suggesting phosphorylation plays a role in ALIX autoinhibition. Yet, the molecular details of these interactions remain unclear owing to challenges relating to characterizing the large, disordered proline-rich domain (PRD) of ALIX.