title: Accumulation of beta (m), a structural member of X,K-ATPase beta-subunit family, in nuclear envelopes of perinatal myocytes.
abstract: Recently discovered muscle-specific beta(m) protein is structurally closely related to the X,K-ATPase beta-subunits. However, it has a number of unique properties such as predominant localization in intracellular stores and lack of association with known X,K-ATPase alpha-subunits on heterologous coexpression. In this study, the primary structure of mouse beta(m) was determined and developmental regulation of the gene (ATP1B4) was analyzed. The expression is first detected at day 14 of gestation, is sharply increased at day 16, and reaches its maximum at day 18. After birth, the expression quickly decreases and is hardly detectable in adult mice. A more detailed subcellular localization study was undertaken, and its results indicate that beta(m) not only is located in sarcoplasmic reticulum but is concentrated in nuclear envelopes of both prenatal and postnatal skeletal muscles. Immunohistochemical studies show that beta(m) is specific to myocytes and, at the subcellular level, many nuclear envelopes are intensively labeled in both fetal and newborn skeletal muscles. Accordingly, beta(m) is detected by immunoblotting in purified nuclei and nuclear membranes from neonatal skeletal muscles. On transfection of human rhabdomyosarcoma cell line RD, green fluorescent protein-tagged beta(m) resides intracellularly with significant enrichment in nuclear envelopes, whereas beta(m) with transmembrane domain deleted localizes in both cytoplasm and nucleoplasm. Nuclear beta(m) apparently is not in association with Na,K-ATPase because we never detected its alpha-subunit in myonuclear membranes. These results indicate that beta(m) has a specialized function in mammalian perinatal myocytes, different from functions of other X,K-ATPase beta-subunits. The unique temporospatial distribution of beta(m) protein expression suggests its important role in development of growing skeletal muscle.
authors.affiliation: Department of Pharmacology, Medical College of Ohio, Toledo, OH 43614, USA.
authors.forename: Hao
authors.initials: H
authors.lastname: Zhao
authors.forename: Nikolay B
authors.initials: NB
authors.lastname: Pestov
authors.forename: Tatyana V
authors.initials: TV
authors.lastname: Korneenko
authors.forename: Mikhail I
authors.initials: MI
authors.lastname: Shakhparonov
authors.forename: Nikolai N
authors.initials: NN
authors.lastname: Modyanov
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics* / Q000378:metabolism; D000367:Age Factors; D000595:Amino Acid Sequence; D000818:Animals; D000831:Animals, Newborn; D018076:DNA, Complementary; D005260:Female; D018507:Gene Expression Regulation, Developmental; D049452:Green Fluorescent Proteins; D007150:Immunohistochemistry; D008164:Luminescent Proteins / Q000235:genetics; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D018485:Muscle Fibers, Skeletal / Q000502:physiology*; D018482:Muscle, Skeletal / Q000166:cytology / Q000254:growth & development / Q000502:physiology*; D009685:Nuclear Envelope / Q000378:metabolism*; D051381:Rats; D000254:Sodium-Potassium-Exchanging ATPase; D013552:Swine; D014157:Transcription Factors; D014162:Transfection
chemical_list: D018076:DNA, Complementary; D008164:Luminescent Proteins; D008562:Membrane Glycoproteins; D014157:Transcription Factors; D049452:Green Fluorescent Proteins; D000251:Adenosine Triphosphatases; C483736:Atp1b4 protein, mouse; D000254:Sodium-Potassium-Exchanging ATPase