title: Mitsugumin 53-mediated maintenance of K+ currents in cardiac myocytes.
abstract: Mitsugumin 53 (MG53) is a muscle-specific RBCC/TRIM family member predominantly localized on small vesicles underneath the plasma membrane. Upon cell-surface lesion MG53 recruits the vesicles to the repair site in an oxidation-dependent manner and MG53-knockout mice develop progressive myopathy associated with defective membrane repair. In this report, we focus on MG53-knockout cardiomyocytes showing abnormal action potential profile and a reduced K+ current density. In cDNA expression experiments using cultured cells, KV2.1-mediated currents were remarkably increased by MG53 without affecting the total and cell-surface levels of channel expression. In imaging analysis MG53 seemed to facilitate the mobility of KV2.1-containing endocytic vesicles with acidic pH. However, similar effects on the current density and vesicular mobility were not observed in the putative dominant-negative form of MG53. Our data suggest that MG53 is involved in a constitutive cycle of certain cell-surface proteins between the plasma membrane and endosome-like vesicles in striated muscle, and also imply that the vesicular dynamics are essential for the quality control of KV2.1 in cardiomyocytes.
authors.affiliation: Department of Medical Chemistry, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Haruko
authors.initials: H
authors.lastname: Masumiya
authors.forename: Yasuhide
authors.initials: Y
authors.lastname: Asaumi
authors.forename: Miyuki
authors.initials: M
authors.lastname: Nishi
authors.forename: Susumu
authors.initials: S
authors.lastname: Minamisawa
authors.forename: Satomi
authors.initials: S
authors.lastname: Adachi-Akahane
authors.forename: Morikatsu
authors.initials: M
authors.lastname: Yoshida
authors.forename: Kenji
authors.initials: K
authors.lastname: Kangawa
authors.forename: Kenta
authors.initials: K
authors.lastname: Ito
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Kagaya
authors.forename: Teruyuki
authors.initials: T
authors.lastname: Yanagisawa
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Yamazaki
authors.forename: Jianjie
authors.initials: J
authors.lastname: Ma
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takeshima
mesh_terms: D000200:Action Potentials; D000818:Animals; D020746:Calcium Channels, L-Type / Q000378:metabolism; D009202:Cardiomyopathies / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism*; D002478:Cells, Cultured; D011992:Endosomes / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008565:Membrane Proteins; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D032383:Myocytes, Cardiac / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism*; D021381:Protein Transport; D051669:Shab Potassium Channels / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D014162:Transfection
chemical_list: D020746:Calcium Channels, L-Type; D002352:Carrier Proteins; C496990:Kcnb1 protein, mouse; C538824:MG53 protein, mouse; D008565:Membrane Proteins; D051669:Shab Potassium Channels; D011188:Potassium