Mitsugumin 53-mediated maintenance of K+ currents in cardiac myocytes.
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.
Masumiya
Haruko
H
Department of Medical Chemistry, Tohoku University Graduate School of Medicine, Sendai, Japan.
Asaumi
Yasuhide
Y
Nishi
Miyuki
M
Minamisawa
Susumu
S
Adachi-Akahane
Satomi
S
Yoshida
Morikatsu
M
Kangawa
Kenji
K
Ito
Kenta
K
Kagaya
Yutaka
Y
Yanagisawa
Teruyuki
T
Yamazaki
Tetsuo
T
Ma
Jianjie
J
Takeshima
Hiroshi
H
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
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