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

Yi Heng Hao, Jennifer M. Doyle, Saumya Ramanathan, Timothy S. Gomez, Da Jia, Ming Xu, Zhijian J. Chen, Daniel D. Billadeau, Michael K. Rosen, Patrick Ryan Potts

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)1051-1064
Number of pages14
JournalCell
Volume152
Issue number5
DOIs
StatePublished - Feb 28 2013

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Ubiquitination
Protein Transport
Ligases
Ubiquitin
Polymerization
Actins
Nucleation
Ubiquitin-Conjugating Enzymes
Pathogens
Proteins
Ubiquitin-Protein Ligases
Endosomes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Hao, Y. H., Doyle, J. M., Ramanathan, S., Gomez, T. S., Jia, D., Xu, M., ... Potts, P. R. (2013). Regulation of WASH-dependent actin polymerization and protein trafficking by ubiquitination. Cell, 152(5), 1051-1064. https://doi.org/10.1016/j.cell.2013.01.051

Regulation of WASH-dependent actin polymerization and protein trafficking by ubiquitination. / Hao, Yi Heng; Doyle, Jennifer M.; Ramanathan, Saumya; Gomez, Timothy S.; Jia, Da; Xu, Ming; Chen, Zhijian J.; Billadeau, Daniel D.; Rosen, Michael K.; Potts, Patrick Ryan.

In: Cell, Vol. 152, No. 5, 28.02.2013, p. 1051-1064.

Research output: Contribution to journalArticle

Hao, YH, Doyle, JM, Ramanathan, S, Gomez, TS, Jia, D, Xu, M, Chen, ZJ, Billadeau, DD, Rosen, MK & Potts, PR 2013, 'Regulation of WASH-dependent actin polymerization and protein trafficking by ubiquitination', Cell, vol. 152, no. 5, pp. 1051-1064. https://doi.org/10.1016/j.cell.2013.01.051
Hao YH, Doyle JM, Ramanathan S, Gomez TS, Jia D, Xu M et al. Regulation of WASH-dependent actin polymerization and protein trafficking by ubiquitination. Cell. 2013 Feb 28;152(5):1051-1064. https://doi.org/10.1016/j.cell.2013.01.051
Hao, Yi Heng ; Doyle, Jennifer M. ; Ramanathan, Saumya ; Gomez, Timothy S. ; Jia, Da ; Xu, Ming ; Chen, Zhijian J. ; Billadeau, Daniel D. ; Rosen, Michael K. ; Potts, Patrick Ryan. / Regulation of WASH-dependent actin polymerization and protein trafficking by ubiquitination. In: Cell. 2013 ; Vol. 152, No. 5. pp. 1051-1064.
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