PI(3,5)P2 controls endosomal branched actin dynamics by regulating cortactin-actin interactions.
Bottom Line: These findings suggest that PI(3,5)P2 formation on endosomes may remove cortactin from endosome-associated branched actin.Conversely, inhibition of Arp2/3 complex activity greatly reduced cortactin localization to late 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.
Affiliation: Department of Cancer Biology, Vanderbilt University Medical Center, Nashville, TN 37232.Show MeSH
Related in: MedlinePlus
License 1 - License 2
Mentions: One mechanism by which cortactin could promote accumulation of actin on endosomes is by regulating branched actin network assembly by the Arp2/3 complex (Uruno et al., 2001; Weaver et al., 2001). To determine whether Arp2/3-mediated branched actin nucleation is required for recruiting cortactin to endosomal membranes, we treated cells with the Arp2/3 complex inhibitor CK-666 (Nolen et al., 2009; Hetrick et al., 2013). Treatment with CK-666 resulted in significantly reduced cortactin localization on Rab7+ endosomes (Fig. 4, A and B). Moreover, the accumulation of cortactin that occurs with inhibition of PI(3,5)P2 synthesis by YM201636 was abolished in CK-666–treated cells. Likewise, Arp2/3 inhibition with CK-666 treatment inhibited actin accumulation on Rab7+ late endosomes in both control and YM201636-treated cells (Fig. 4, A and C). These data suggest a model in which cortactin is recruited to late endosomes by interactions with branched actin networks and removed by interaction with PI(3,5)P2.
Affiliation: Department of Cancer Biology, Vanderbilt University Medical Center, Nashville, TN 37232.