MG53 nucleates assembly of cell membrane repair machinery

Chuanxi Cai; Haruko Masumiya; Noah Weisleder; Noriyuki Matsuda; Miyuki Nishi; Moonsun Hwang; Jae Kyun Ko; Peihui Lin; Angela Thornton; Xiaoli Zhao; Zui Pan; Shinji Komazaki; Marco Brotto; Hiroshi Takeshima; Jianjie Ma

doi:10.1038/ncb1812

MG53 nucleates assembly of cell membrane repair machinery

Chuanxi Cai, Haruko Masumiya, Noah Weisleder, Noriyuki Matsuda, Miyuki Nishi, Moonsun Hwang, Jae Kyun Ko, Peihui Lin, Angela Thornton, Xiaoli Zhao, Zui Pan, Shinji Komazaki, Marco Brotto, Hiroshi Takeshima, Jianjie Ma

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

411 Scopus citations

Abstract

Dynamic membrane repair and remodelling is an elemental process that maintains cell integrity and mediates efficient cellular function. Here we report that MG53, a muscle-specific tripartite motif family protein (TRIM72), is a component of the sarcolemmal membrane-repair machinery. MG53 interacts with phosphatidylserine to associate with intracellular vesicles that traffic to and fuse with sarcolemmal membranes. Mice null for MG53 show progressive myopathy and reduced exercise capability, associated with defective membrane-repair capacity. Injury of the sarcolemmal membrane leads to entry of the extracellular oxidative environment and MG53 oligomerization, resulting in recruitment of MG53-containing vesicles to the injury site. After vesicle translocation, entry of extracellular Ca²⁺ facilitates vesicle fusion to reseal the membrane. Our data indicate that intracellular vesicle translocation and Ca²⁺-dependent membrane fusion are distinct steps involved in the repair of membrane damage and that MG53 may initiate the assembly of the membrane repair machinery in an oxidation-dependent manner.

Original language	English
Pages (from-to)	56-64
Number of pages	9
Journal	Nature Cell Biology
Volume	11
Issue number	1
DOIs	https://doi.org/10.1038/ncb1812
State	Published - 2009

Funding

We thank Michael Reid, Jerome Parness, and Heping Cheng for helpful suggestions to this work. Yi Chu provided assistance in data processing and graphic conversions. We also thank the Cancer Institute of New Jersey Tissue Analytic Services Shared Resource and the UMDNJ-Cell Imaging Core facility, which is supported by NCRR from NIH, for providing assistance with imaging. This work was supported by grants from NIH (J.M.), Ministry of Education, Science, Sports and Culture of Japan (H.T.) and the American Heart Association (C.C., N.W., M.B.).

Funders	Funder number
National Institutes of Health (NIH)
National Heart, Lung, and Blood Institute Family Blood Pressure Program	R01HL069000
National Heart, Lung, and Blood Institute Family Blood Pressure Program
National Center for Research Resources
American the American Heart Association
Rutgers Cancer Institute of New Jersey and Rutgers University
Ministry of Education, Culture, Sports, Science and Technology

ASJC Scopus subject areas

Cell Biology

Access to Document

10.1038/ncb1812

Cite this

@article{76ae1e2f649e47a285a18b04f5c3292f,

title = "MG53 nucleates assembly of cell membrane repair machinery",

abstract = "Dynamic membrane repair and remodelling is an elemental process that maintains cell integrity and mediates efficient cellular function. Here we report that MG53, a muscle-specific tripartite motif family protein (TRIM72), is a component of the sarcolemmal membrane-repair machinery. MG53 interacts with phosphatidylserine to associate with intracellular vesicles that traffic to and fuse with sarcolemmal membranes. Mice null for MG53 show progressive myopathy and reduced exercise capability, associated with defective membrane-repair capacity. Injury of the sarcolemmal membrane leads to entry of the extracellular oxidative environment and MG53 oligomerization, resulting in recruitment of MG53-containing vesicles to the injury site. After vesicle translocation, entry of extracellular Ca2+ facilitates vesicle fusion to reseal the membrane. Our data indicate that intracellular vesicle translocation and Ca2+-dependent membrane fusion are distinct steps involved in the repair of membrane damage and that MG53 may initiate the assembly of the membrane repair machinery in an oxidation-dependent manner.",

author = "Chuanxi Cai and Haruko Masumiya and Noah Weisleder and Noriyuki Matsuda and Miyuki Nishi and Moonsun Hwang and Ko, \{Jae Kyun\} and Peihui Lin and Angela Thornton and Xiaoli Zhao and Zui Pan and Shinji Komazaki and Marco Brotto and Hiroshi Takeshima and Jianjie Ma",

year = "2009",

doi = "10.1038/ncb1812",

language = "English",

volume = "11",

pages = "56--64",

number = "1",

}

TY - JOUR

T1 - MG53 nucleates assembly of cell membrane repair machinery

AU - Cai, Chuanxi

AU - Masumiya, Haruko

AU - Weisleder, Noah

AU - Matsuda, Noriyuki

AU - Nishi, Miyuki

AU - Hwang, Moonsun

AU - Ko, Jae Kyun

AU - Lin, Peihui

AU - Thornton, Angela

AU - Zhao, Xiaoli

AU - Pan, Zui

AU - Komazaki, Shinji

AU - Brotto, Marco

AU - Takeshima, Hiroshi

AU - Ma, Jianjie

PY - 2009

Y1 - 2009

N2 - Dynamic membrane repair and remodelling is an elemental process that maintains cell integrity and mediates efficient cellular function. Here we report that MG53, a muscle-specific tripartite motif family protein (TRIM72), is a component of the sarcolemmal membrane-repair machinery. MG53 interacts with phosphatidylserine to associate with intracellular vesicles that traffic to and fuse with sarcolemmal membranes. Mice null for MG53 show progressive myopathy and reduced exercise capability, associated with defective membrane-repair capacity. Injury of the sarcolemmal membrane leads to entry of the extracellular oxidative environment and MG53 oligomerization, resulting in recruitment of MG53-containing vesicles to the injury site. After vesicle translocation, entry of extracellular Ca2+ facilitates vesicle fusion to reseal the membrane. Our data indicate that intracellular vesicle translocation and Ca2+-dependent membrane fusion are distinct steps involved in the repair of membrane damage and that MG53 may initiate the assembly of the membrane repair machinery in an oxidation-dependent manner.

AB - Dynamic membrane repair and remodelling is an elemental process that maintains cell integrity and mediates efficient cellular function. Here we report that MG53, a muscle-specific tripartite motif family protein (TRIM72), is a component of the sarcolemmal membrane-repair machinery. MG53 interacts with phosphatidylserine to associate with intracellular vesicles that traffic to and fuse with sarcolemmal membranes. Mice null for MG53 show progressive myopathy and reduced exercise capability, associated with defective membrane-repair capacity. Injury of the sarcolemmal membrane leads to entry of the extracellular oxidative environment and MG53 oligomerization, resulting in recruitment of MG53-containing vesicles to the injury site. After vesicle translocation, entry of extracellular Ca2+ facilitates vesicle fusion to reseal the membrane. Our data indicate that intracellular vesicle translocation and Ca2+-dependent membrane fusion are distinct steps involved in the repair of membrane damage and that MG53 may initiate the assembly of the membrane repair machinery in an oxidation-dependent manner.

UR - https://www.scopus.com/pages/publications/58149326805

UR - https://www.scopus.com/inward/citedby.url?scp=58149326805&partnerID=8YFLogxK

U2 - 10.1038/ncb1812

DO - 10.1038/ncb1812

M3 - Article

C2 - 19043407

AN - SCOPUS:58149326805

SN - 1465-7392

VL - 11

SP - 56

EP - 64

JO - Nature Cell Biology

JF - Nature Cell Biology

IS - 1

ER -

MG53 nucleates assembly of cell membrane repair machinery

Abstract

Funding

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this