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

doi:10.1016/j.cell.2013.01.051

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

Oncology

Research output: Contribution to journal › Article › peer-review

129 Scopus citations

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 language	English (US)
Pages (from-to)	1051-1064
Number of pages	14
Journal	Cell
Volume	152
Issue number	5
DOIs	https://doi.org/10.1016/j.cell.2013.01.051
State	Published - Feb 28 2013

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

Access to Document

10.1016/j.cell.2013.01.051

Cite this

@article{e171f25260674f02bfa36e9ac781df0c,

title = "Regulation of WASH-dependent actin polymerization and protein trafficking by ubiquitination",

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.",

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

note = "Funding Information: We thank Mitsuaki Tabuchi (Kawasaki Medical School, Japan) for providing the retromer construct. We also thank Potts lab members for helpful discussions and critical reading of the manuscript. This work was supported by the Cancer Prevention and Research Initiative of Texas R1117 (P.R.P.), Department of Defense CA110261 (P.R.P.), Howard Hughes Medical Institute (M.K.R.), Mayo Foundation (D.D.B.), Michael L. Rosenberg Scholar in Medical Research fund (P.R.P.), NIH R01-AI065474 (D.D.B.), NIH R01-GM063692 (Z.J.C.), NIH R01-GM56322 (M.K.R.), Sara and Frank McKnight Fellowship (P.R.P.), and Welch Foundation I–1544 (M.K.R.) and I-1389 (Z.J.C.). ",

year = "2013",

month = feb,

day = "28",

doi = "10.1016/j.cell.2013.01.051",

language = "English (US)",

volume = "152",

pages = "1051--1064",

journal = "Cell",

issn = "0092-8674",

publisher = "Cell Press",

number = "5",

}

TY - JOUR

T1 - Regulation of WASH-dependent actin polymerization and protein trafficking by ubiquitination

AU - Hao, Yi Heng

AU - Doyle, Jennifer M.

AU - Ramanathan, Saumya

AU - Gomez, Timothy S.

AU - Jia, Da

AU - Xu, Ming

AU - Chen, Zhijian J.

AU - Billadeau, Daniel D.

AU - Rosen, Michael K.

AU - Potts, Patrick Ryan

N1 - Funding Information: We thank Mitsuaki Tabuchi (Kawasaki Medical School, Japan) for providing the retromer construct. We also thank Potts lab members for helpful discussions and critical reading of the manuscript. This work was supported by the Cancer Prevention and Research Initiative of Texas R1117 (P.R.P.), Department of Defense CA110261 (P.R.P.), Howard Hughes Medical Institute (M.K.R.), Mayo Foundation (D.D.B.), Michael L. Rosenberg Scholar in Medical Research fund (P.R.P.), NIH R01-AI065474 (D.D.B.), NIH R01-GM063692 (Z.J.C.), NIH R01-GM56322 (M.K.R.), Sara and Frank McKnight Fellowship (P.R.P.), and Welch Foundation I–1544 (M.K.R.) and I-1389 (Z.J.C.).

PY - 2013/2/28

Y1 - 2013/2/28

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84874765742&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84874765742&partnerID=8YFLogxK

U2 - 10.1016/j.cell.2013.01.051

DO - 10.1016/j.cell.2013.01.051

M3 - Article

C2 - 23452853

AN - SCOPUS:84874765742

SN - 0092-8674

VL - 152

SP - 1051

EP - 1064

JO - Cell

JF - Cell

IS - 5

ER -

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

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this