Immuno-proteomic approach to excitation–contraction coupling in skeletal and cardiac muscle: Molecular insights revealed by the mitsugumins

Weisleder, Noah; Takeshima, Hiroshi; Ma, Jianjie

doi:10.1016/j.ceca.2007.10.006

Cited by 59 publications

(53 citation statements)

References 70 publications

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“…Recent studies have also indicated a role for TRIM proteins in defense against events involving membrane penetration, such as protection against infection by various viruses, including human immunodeficiency virus (13-15). Although most of the studies concentrate on the cytosolic action of TRIM, limited reports have investigated the role of TRIM proteins in membrane signaling or recycling.We have previously established an immunoproteomics approach that allows definition of novel components involved in myogenesis, Ca 2ϩ signaling, and maintenance of membrane integrity in striated muscle (16). Using this approach, we have shown that junctophilin is a structural protein that establishes functional communication between sarcoplasmic reticulum and transverse tubule membranes at triad and dyad junctions in striated muscle (17)(18)(19).…”

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confidence: 99%

“…We have previously established an immunoproteomics approach that allows definition of novel components involved in myogenesis, Ca 2ϩ signaling, and maintenance of membrane integrity in striated muscle (16). Using this approach, we have shown that junctophilin is a structural protein that establishes functional communication between sarcoplasmic reticulum and transverse tubule membranes at triad and dyad junctions in striated muscle (17)(18)(19).…”

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confidence: 99%

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MG53 Regulates Membrane Budding and Exocytosis in Muscle Cells

Cai

Masumiya

Weisleder

et al. 2009

Journal of Biological Chemistry

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104

134

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Membrane recycling and remodeling contribute to multiple cellular functions, including cell fusion events during myogenesis. We have identified a tripartite motif (TRIM72) family member protein named MG53 and defined its role in mediating the dynamic process of membrane fusion and exocytosis in striated muscle. MG53 is a muscle-specific protein that contains a TRIM motif at the amino terminus and a SPRY motif at the carboxyl terminus. Live cell imaging of green fluorescent protein-MG53 fusion construct in cultured myoblasts showed that although MG53 contains no transmembrane segment it is tightly associated with intracellular vesicles and sarcolemmal membrane. RNA interference-mediated knockdown of MG53 expression impeded myoblast differentiation, whereas overexpression of MG53 enhanced vesicle trafficking to and budding from sarcolemmal membrane. Co-expression studies indicated that MG53 activity is regulated by a functional interaction with caveolin-3. Our data reveal a new function for TRIM family proteins in regulating membrane trafficking and fusion in striated muscles.When myoblasts exit the cell cycle during myogenesis, dramatic changes in membrane organization occur as myoblast fusion allows the formation of multinucleated muscle fibers. In addition to cell fusion events, differentiation of myotubes involves establishment of specialized membrane structures (1, 2). The transverse tubular invagination of sarcolemmal membrane and the intracellular membrane network known as the sarcoplasmic reticulum are two highly organized membrane architectures in cardiac and skeletal muscle. Establishment of these intricate membrane compartments requires extensive remodeling of the immature myoblast membranes. Dynamic membrane remodeling also contributes to many physiologic processes in mature muscle, including Ca 2ϩ signaling, trafficking of glucose transporter (GLUT4), and other membrane internalization events involving caveolae structures (3-6). Although defects in membrane integrity have been linked to various forms of muscular dystrophy (7,8), the molecular machinery regulating these specific membrane recycling and remodeling events in striated muscle is not well defined.The large tripartite motif (TRIM) 5 family of proteins is involved in numerous cellular functions in a wide variety of cell types. Members of this protein family contain signature motifs that include a RING finger, a zinc binding moiety (B-box), and a coiled coil structure (RBCC), which invariably comprise the amino-terminal domain of TRIM family members (9). The carboxyl-terminal sequence of TRIM proteins is variable; in some cases a subfamily of TRIM proteins contains a SPRY domain, a sequence first observed in the ryanodine receptor Ca 2ϩ channel in the sarcoplasmic reticulum membrane of excitable cells (10). Extensive studies have revealed that protein-protein interactions in the cytosol mediate the defined functions of TRIM proteins. For example, the ubiquitin E3 ligase enzymatic activity of several TRIM family members requires the B-box motif ...

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MG53 Regulates Membrane Budding and Exocytosis in Muscle Cells

Cai

Masumiya

Weisleder

et al. 2009

Journal of Biological Chemistry

Self Cite

104

134

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“…12 Thought screening of our unique immunoproteomic monoclonal antibody targeting membrane-associated proteins found in striated muscle, 15 we identified a monoclonal antibody (mAb 5259) that would recognize the subsarcolemmal space and the gap within the triad junction. Immunoaffinity purification with this antibody produced a protein of 53 kDa that we named MG53.…”

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confidence: 99%

Mitsugumin 53 (MG53) facilitates vesicle trafficking in striated muscle to contribute to cell membrane repair

Weisleder¹,

Takeshima²,

Ma³

2009

Communicative & Integrative Biology

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“…Aside the RyR1, the junctional sarcoplasmic reticulum is enriched in several other proteins including the structural proteins triadin and junctin, as well as minor constituents such as JP-45, junctate and humbug, mitsugumin-29, SRP-27/TRIC-A and junctophilin-1 [4,[27][28][29]. These minor constituents play a role in the fine regulation of Ca 2+ release from the SR or are involved in maintaining the structural integrity of the Ca 2+ release machinery.…”

Section: Excitation-contraction Couplingmentioning

confidence: 99%

Ca2+ handling abnormalities in early-onset muscle diseases: Novel concepts and perspectives

Treves

Jungbluth

Voermans

et al. 2017

Seminars in Cell & Developmental Biology

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a b s t r a c tThe physiological process by which Ca 2+ is released from the sarcoplasmic reticulum is called excitationcontraction coupling; it is initiated by an action potential which travels deep into the muscle fiber where it is sensed by the dihydropyridine receptor, a voltage sensing L-type Ca 2+ channel localized on the transverse tubules. Voltage-induced conformational changes in the dihydropyridine receptor activate the ryanodine receptor Ca 2+ release channel of the sarcoplasmic reticulum. The released Ca 2+ binds to troponin C, enabling contractile thick-thin filament interactions. The Ca 2+ is subsequently transported back into the sarcoplasmic reticulum by specialized Ca 2+ pumps (SERCA), preparing the muscle for a new cycle of contraction. Although other proteins are involved in excitation-contraction coupling, the mechanism described above emphasizes the unique role played by the two Ca 2+ channels (the dihydropyridine receptor and the ryanodine receptor), the SERCA Ca 2+ pumps and the exquisite spatial organization of the membrane compartments endowed with the proteins responsible for this mechanism to function rapidly and efficiently. Research over the past two decades has uncovered the fine details of excitation-contraction coupling under normal conditions while advances in genomics have helped to identify mutations in novel genes in patients with neuromuscular disorders. While it is now clear that many patients with congenital muscle diseases carry mutations in genes encoding proteins directly involved in Ca 2+ homeostasis, it has become apparent that mutations are also present in genes encoding for proteins not thought to be directly involved in Ca 2+ regulation. Ongoing research in the field now focuses on understanding the functional effect of individual mutations, as well as understanding the role of proteins not specifically located in the sarcoplasmic reticulum which nevertheless are involved in Ca 2+ regulation or excitation-contraction coupling. The principal challenge for the future is the identification of drug targets that can be pharmacologically manipulated by small molecules, with the ultimate aim to improve muscle function and quality of life of patients with congenital muscle disorders. The aim of this review is to give an overview of the most recent findings concerning Ca 2+ dysregulation and its impact on muscle function in patients with congenital muscle disorders due to mutations in proteins involved in excitation-contraction coupling and more broadly on Ca 2+ homeostasis.

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Immuno-proteomic approach to excitation–contraction coupling in skeletal and cardiac muscle: Molecular insights revealed by the mitsugumins

Cited by 59 publications

References 70 publications

MG53 Regulates Membrane Budding and Exocytosis in Muscle Cells

MG53 Regulates Membrane Budding and Exocytosis in Muscle Cells

Mitsugumin 53 (MG53) facilitates vesicle trafficking in striated muscle to contribute to cell membrane repair

Ca2+ handling abnormalities in early-onset muscle diseases: Novel concepts and perspectives

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