MYO6 Regulates Spatial Organization of Signaling Endosomes Driving AKT Activation and Actin Dynamics

Publication date: 6 June 2017
Source:Cell Reports, Volume 19, Issue 10
Author(s): Thomas A. Masters, David A. Tumbarello, Margarita V. Chibalina, Folma Buss
APPL1- and RAB5-positive signaling endosomes play a crucial role in the activation of AKT in response to extracellular stimuli. Myosin VI (MYO6) and two of its cargo adaptor proteins, GIPC and TOM1/TOM1L2, localize to these peripheral endosomes and mediate endosome association with cortical actin filaments. Loss of MYO6 leads to the displacement of these endosomes from the cell cortex and accumulation in the perinuclear space. Depletion of this myosin not only affects endosome positioning, but also induces actin and lipid remodeling consistent with endosome maturation, including accumulation of F-actin and the endosomal lipid PI(3)P. These processes acutely perturb endosome function, as both AKT phosphorylation and RAC-dependent membrane ruffling were markedly reduced by depletion of either APPL1 or MYO6. These results place MYO6 and its binding partners at a central nexus in cellular signaling linking actin dynamics at the cell surface and endosomal signaling in the cell cortex.

Graphical abstract

Teaser

Masters et al. report that MYO6 tethers APPL1 signaling endosomes to the actin cortex. Depletion of MYO6 leads to premature maturation and displacement of these endosomes away from the cell cortex, as well as defective AKT activation and impaired cortical actin dynamics.


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