MYO6 regulates spatial organization of signaling endosomes driving AKT activation and actin dynamics
MYO6 regulates spatial organization of signaling endosomes driving AKT activation and actin dynamics
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.
2088-2101
Masters, Thomas A.
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Tumbarello, David A.
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Chibalina, Margarita V.
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Buss, Folma
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6 June 2017
Masters, Thomas A.
48e2adb9-13bf-48d2-a210-d28da6e3c1fd
Tumbarello, David A.
75c6932e-fdbf-4d3c-bb4f-48fbbdba93a2
Chibalina, Margarita V.
4ba99462-6821-4aab-bcbb-5b5f42cea248
Buss, Folma
aaa13580-8f07-4a7d-b469-54aceba78a06
Masters, Thomas A., Tumbarello, David A., Chibalina, Margarita V. and Buss, Folma
(2017)
MYO6 regulates spatial organization of signaling endosomes driving AKT activation and actin dynamics.
Cell Reports, 19 (10), .
(doi:10.1016/j.celrep.2017.05.048).
Abstract
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.
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Accepted/In Press date: 12 May 2017
e-pub ahead of print date: 6 June 2017
Published date: 6 June 2017
Organisations:
Academic
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Local EPrints ID: 411111
URI: http://eprints.soton.ac.uk/id/eprint/411111
ISSN: 2211-1247
PURE UUID: ff4c13d7-6e74-4d1b-997f-e4a5e122e5c5
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Date deposited: 14 Jun 2017 16:31
Last modified: 16 Mar 2024 04:18
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Author:
Thomas A. Masters
Author:
Margarita V. Chibalina
Author:
Folma Buss
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