PI(3,5)P2 controls endosomal branched actin dynamics by regulating cortactin-actin interactions.

Hong NH, Qi A, Weaver AM
J Cell Biol. 2015 210 (5): 753-69

PMID: 26323691 · PMCID: PMC4555817 · DOI:10.1083/jcb.201412127

Branched actin critically contributes to membrane trafficking by regulating membrane curvature, dynamics, fission, and transport. However, how actin dynamics are controlled at membranes is poorly understood. Here, we identify the branched actin regulator cortactin as a direct binding partner of phosphatidylinositol 3,5-bisphosphate (PI(3,5)P2) and demonstrate that their interaction promotes turnover of late endosomal actin. In vitro biochemical studies indicated that cortactin binds PI(3,5)P2 via its actin filament-binding region. Furthermore, PI(3,5)P2 competed with actin filaments for binding to cortactin, thereby antagonizing cortactin activity. These findings suggest that PI(3,5)P2 formation on endosomes may remove cortactin from endosome-associated branched actin. Indeed, inhibition of PI(3,5)P2 production led to cortactin accumulation and actin stabilization on Rab7(+) endosomes. Conversely, inhibition of Arp2/3 complex activity greatly reduced cortactin localization to late endosomes. Knockdown of cortactin reversed PI(3,5)P2-inhibitor-induced actin accumulation and stabilization on endosomes. These data suggest a model in which PI(3,5)P2 binding removes cortactin from late endosomal branched actin networks and thereby promotes net actin turnover.

© 2015 Hong et al.

MeSH Terms (16)

Actin-Related Protein 2-3 Complex Actins Binding Sites Cell Line, Tumor Cortactin Endosomes Enzyme Activation HeLa Cells Humans Phosphatidylinositol Phosphates Protein Binding Protein Structure, Tertiary rab GTP-Binding Proteins RNA, Small Interfering RNA Interference Wiskott-Aldrich Syndrome Protein, Neuronal

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