Phosphorylation-Dependent Activation of the ESCRT Function of ALIX in Cytokinetic Abscission and Retroviral Budding

• Cytosolic ALIX changes from closed to open conformation during M phase induction
• Phosphorylation of the S718-S721 residues produces an open conformation of ALIX
• S718-S721 phosphorylation allows ALIX to function in cytokinetic abscission
• S718-S721 phosphorylation is required for ALIX to support EIAV budding

SummaryThe modular adaptor protein ALIX is a key player in multiple ESCRT-III-mediated membrane remodeling processes. ALIX is normally present in a closed conformation due to an intramolecular interaction that renders ALIX unable to perform its ESCRT functions. Here we demonstrate that M phase-specific phosphorylation of the intramolecular interaction site within the proline-rich domain (PRD) of ALIX transforms cytosolic ALIX from closed to open conformation. Defining the role of this mechanism of ALIX regulation in three classical ESCRT-mediated processes revealed that phosphorylation of the intramolecular interaction site in the PRD is required for ALIX to function in cytokinetic abscission and retroviral budding, but not in multivesicular body sorting of activated epidermal growth factor receptor. Thus, phosphorylation of the intramolecular interaction site in the PRD is one of the major mechanisms that activates the ESCRT function of ALIX.

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