TRIM-edicine

MG53 and cell membrane repair

MG53, belonging to the TRIM family of proteins, is the first known essential molecular component in the intrinsic cellular membrane repair process. Following instances of membrane damage, the entry of the oxidative extracellular environment results in MG53 oligomerization and translocation of MG53-containing vesicle to the injury site to initiate membrane repair. Muscle fibers lacking in MG53 display defective membrane permeability and increased susceptibility to disease, suggesting that MG53 is a critical component of the membrane repair process. Through either the administration of recombinant MG53 protein or pharmacological modulation of endogenous MG53, TRIM-edicine believes it possesses a potentially important therapeutic agent/opportunity targeting several attractive markets involving tissue damage, including acute pulmonary injury, muscular dystrophy, and dermal wounds.

MG53

MG53 (in green) acts to repair membrane damage produced by physical injury to the cell (indicated by arrow). A membrane patch is formed at the site of injury (a). In the case of extensive damage that breaks the cell membrane, MG53 also functions to repair cellular damage (b).

Publications

  • Hwang M, Ko JK, Weisleder N, Takeshima H, Ma J. Redox-dependent oligomerization through a leucine-zipper motif is essential for MG53-mediated cell membrane repair. Am J Physiol Cell Physiol July 2011 301(1): C106-C114.

    Lin P, Zhu H, Cai C, Weisleder N, Takeshima H, Ma J. Non-muscle myosin IIA facilitates vesicle trafficking for MG53-mediated cell membrane repair. Biophysical Journal, 100(3) 2 February 2011

    Waddell LB, Lemckert FA, Zheng XF, Tran J, Evesson FJ, Hawkes JM, 1, Lek A, Street NE, Lin P, Clarke NF, Landstrom AP, Ackerman MJ, Weisleder N, Ma J, North KN, Cooper ST. Dysferlin, Annexin A1 and MG53 are upregulated in muscular dystrophy and localise to longitudinal tubules of the t-system with stretch. J Neuropathol Exp Neurol. 2011 Apr; 70(4):302-13.

    Zhu H, Lin P, De G, Choi KH, Takeshima H, Weisleder N, Ma J. PTRF anchors MG53 to cell injury site for initiation of membrane repair. J Biol Chem. 2011 Feb 22. Selected for the Paper of the Week

    Zhang Y, Li F, Jin L, Peng W, Song R, Ma J, Cao CM, Xiao RP. MG53 participates in ischaemic postconditioning through the RISK signalling pathway. Cardiovasc Res. 2011 Feb 24.

    Cao, CM*, Zhang Y*, Weisleder N*, Ferrante C, Wang, X, Lu F, Zhang, Y, Song R, Hwang M, Jin L, Guo Y, Peng W, Li G, Nishi M, Takeshima H, Ma J, Xiao RP. MG53 Constitutes a Primary Determinant of Cardiac Ischemic Preconditioning. Circulation. 2010 Jun 15;121(23):2565-74. (* Equal contributors)

    Wang X, Xie W, Zhang Y, Lin P, Han L, Han P, Wang Y, Chen Z, Ji G, Zheng M, Weisleder N, Xiao RP, Takeshima H, Ma J, Cheng H. Cardioprotection of Ischemia/Reperfusion Injury by Cholesterol-Dependent MG53-Mediated Membrane Repair. Circ Res. 2010 Jul 9;107(1):76-83.

    Cai C*, Weisleder N*, Ko JK, Komazaki S, Sunada Y, Nishi M, Takeshima H, Ma J. Membrane repair defects in muscular dystrophy are linked to altered interaction between MG53, caveolin-3 and dysferlin. J Biol Chem. 2009 Jun 5;284(23):15894-902. (* Equal contributors) Selected for the Paper of the Week

    Masumiya H, Asaumi Y, Nishi M, Minamisawa S, Adachi-Akahane S, Yoshida M, Kangawa K, Ito K, Kagaya Y, Yanagisawa T, Yamazaki T, Ma J, Takeshima H. Mitsugumin 53-mediated maintenance of K+ currents in cardiac myocytes. Channels. 2009 Jan-Feb;3(1):6-11.

    Weisleder N, Takeshima H, Ma J. Mitsugumin 53 (MG53) facilitates vesicle trafficking in striated muscle to contribute to cell membrane repair. Communicative & Integrative Biology. 2009 March/April 2(3):1-2. Invited review

    Cai C, Masumiya H, Weisleder N, Matsuda N, Nishi M, Hwang M, Ko JK, Lin P, Thornton A, Zhao X, Pan Z, Komazaki S, Brotto M, Takeshima H, Ma J. MG53 nucleates assembly of cell membrane repair machinery. Nat Cell Biol. 2009 11: 56-64.

    Cai C*, Masumiya H*, Weisleder N*, Pan Z, Nishi M, Komazaki S, Takeshima H, Ma J. MG53 regulates membrane budding and exocytosis in muscle cells. J Biol Chem. 2009 Jan 30;284(5):3314-22. (* Equal contributors)

Patents

  • COMPOSITIONS AND METHODS TO MODULATE CELL MEMBRANE RESEALING. PCT/US2008/085573

    PROTEINS, NUCLEIC ACIDS ENCODING THE SAME AND ASSOCIATED METHODS OF USE. PCT/US2007/015815

    COMPOSITIONS AND METHODS FOR THE TREATMENT AND PREVENTION OF CARDIAC ISCHEMIC INJURY (US/61/318,452)

    SERUM MG53 PROTEIN AS A DIAGNOSTIC MARKER FOR TISSUE INJURY (US/61/410,430)