title: Mitsugumin 53 attenuates the activity of sarcoplasmic reticulum Ca(2+)-ATPase 1a (SERCA1a) in skeletal muscle.
abstract: Mitsugumin 53 (MG53) is a member of the membrane repair system in skeletal muscle. However, the roles of MG53 in the unique functions of skeletal muscle have not been addressed, although it is known that MG53 is expressed only in skeletal and cardiac muscle. In the present study, MG53-binding proteins were examined along with proteins that mediate skeletal muscle contraction and relaxation using the binding assays of various MG53 domains and quadrupole time-of-flight mass spectrometry. MG53 binds to sarcoplasmic reticulum Ca(2+)-ATPase 1a (SERCA1a) via its tripartite motif (TRIM) and PRY domains. The binding was confirmed in rabbit skeletal muscle and mouse primary skeletal myotubes by co-immunoprecipitation and immunocytochemistry. MG53 knockdown in mouse primary skeletal myotubes increased Ca(2+)-uptake through SERCA1a (more than 35%) at micromolar Ca(2+) but not at nanomolar Ca(2+), suggesting that MG53 attenuates SERCA1a activity possibly during skeletal muscle contraction or relaxation but not during the resting state of skeletal muscle. Therefore MG53 could be a new candidate for the diagnosis and treatment of patients with Brody syndrome, which is not related to the mutations in the gene coding for SERCA1a, but still accompanies exercise-induced muscle stiffness and delayed muscle relaxation due to a reduction in SERCA1a activity.
authors.affiliation: Department of Physiology, College of Medicine, The Catholic University of Korea, Seoul 137-701, Republic of Korea.
authors.forename: Keon Jin
authors.initials: KJ
authors.lastname: Lee
authors.forename: Chang Sik
authors.initials: CS
authors.lastname: Park
authors.forename: Jin Seok
authors.initials: JS
authors.lastname: Woo
authors.forename: Do Han
authors.initials: DH
authors.lastname: Kim
authors.forename: Jianjie
authors.initials: J
authors.lastname: Ma
authors.forename: Eun Hui
authors.initials: EH
authors.lastname: Lee
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D047468:Immunoprecipitation; D008565:Membrane Proteins; D051379:Mice; D008969:Molecular Sequence Data; D018485:Muscle Fibers, Skeletal / Q000378:metabolism; D009124:Muscle Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D011510:Proteolipids / Q000378:metabolism; D011817:Rabbits; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000378:metabolism*
chemical_list: C506944:Atp2a1 protein, mouse; D002352:Carrier Proteins; C538824:MG53 protein, mouse; D008565:Membrane Proteins; D009124:Muscle Proteins; D011510:Proteolipids; C077258:sarcolipin; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases