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Cell. 2013 Feb 28;152(5):1051-64. doi: 10.1016/j.cell.2013.01.051.

Regulation of WASH-dependent actin polymerization and protein trafficking by ubiquitination.

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1
Department of Physiology, UT Southwestern Dallas, TX 75390, USA.

Abstract

Endosomal protein trafficking is an essential cellular process that is deregulated in several diseases and targeted by pathogens. Here, we describe a role for ubiquitination in this process. We find that the E3 RING ubiquitin ligase, MAGE-L2-TRIM27, localizes to endosomes through interactions with the retromer complex. Knockdown of MAGE-L2-TRIM27 or the Ube2O E2 ubiquitin-conjugating enzyme significantly impaired retromer-mediated transport. We further demonstrate that MAGE-L2-TRIM27 ubiquitin ligase activity is required for nucleation of endosomal F-actin by the WASH regulatory complex, a known regulator of retromer-mediated transport. Mechanistic studies showed that MAGE-L2-TRIM27 facilitates K63-linked ubiquitination of WASH K220. Significantly, disruption of WASH ubiquitination impaired endosomal F-actin nucleation and retromer-dependent transport. These findings provide a cellular and molecular function for MAGE-L2-TRIM27 in retrograde transport, including an unappreciated role of K63-linked ubiquitination and identification of an activating signal of the WASH regulatory complex.

PMID:
23452853
PMCID:
PMC3640276
DOI:
10.1016/j.cell.2013.01.051
[Indexed for MEDLINE]
Free PMC Article
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