title: Myosin VI localization and expression in striated muscle pathology.
abstract: Myosin VI (MVI) is a unique unconventional myosin translocating, unlike other myosins, towards the minus end of actin filaments. It is involved in numerous cellular processes such as endocytosis, intracellular trafficking, cell migration, and transcription. In mammalian skeletal muscles it localizes mainly to sarcoplasmic reticulum and is also present within the muscle nuclei and at the neuromuscular junction (Karolczak et al. Histochem Cell Biol 2013; 23:219-228). We have also shown that in denervated rat hindlimb muscle the MVI expression level is significantly increased and its localization is changed, indicating an important role of MVI in striated muscle pathology. Here, we addressed this problem by examining the distribution and expression levels of myosin VI in biopsies of skeletal muscles from patients with different myopathies. We found that, particularly in myopathies associated with fiber atrophy, the amount of MVI was enhanced and its localization in affected fibers was changed. Also, since a mutation within the human MVI gene was shown to be associated with cardiomyopathy, we assessed MVI localization and expression level in cardiac muscle using wild type and MLP(-/-) mice, a dilated cardiomyopathy model. No significant difference in MVI expression level was observed for both types of animals. MVI was found at intercalated discs and also at the sarcoplasmic reticulum. In the knockout mice, it was also present in ring-like structures surrounding the nuclei. The data indicate that in striated muscle MVI could be engaged in sarcoplasmic reticulum maintenance and/or functioning, vesicular transport, signal transmission and possibly in gene transcription.
authors.affiliation: Department of Biochemistry, Laboratory of Molecular Basis of Cell Motility, Nencki Institute of Experimental Biology, Warsaw, Poland.
authors.forename: Justyna
authors.initials: J
authors.lastname: Karolczak
authors.forename: Serge
authors.initials: S
authors.lastname: Weis
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Ehler
authors.forename: Biruta
authors.initials: B
authors.lastname: Kierdaszuk
authors.forename: Mariusz
authors.initials: M
authors.lastname: Berdyński
authors.forename: Cezary
authors.initials: C
authors.lastname: Zekanowski
authors.forename: Anna M
authors.initials: AM
authors.lastname: Kamińska
authors.forename: Maria Jolanta
authors.initials: MJ
authors.lastname: Rędowicz
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D001706:Biopsy; D015153:Blotting, Western; D002311:Cardiomyopathy, Dilated / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D060588:LIM Domain Proteins / Q000172:deficiency / Q000235:genetics; D008297:Male; D018345:Mice, Knockout; D008875:Middle Aged; D009124:Muscle Proteins / Q000172:deficiency / Q000235:genetics; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology; D009133:Muscular Atrophy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D018995:Myosin Heavy Chains / Q000378:metabolism*; D012519:Sarcoplasmic Reticulum / Q000378:metabolism
chemical_list: D060588:LIM Domain Proteins; D009124:Muscle Proteins; C090114:cysteine and glycine-rich protein 3; C089785:myosin VI; D018995:Myosin Heavy Chains
keywords: cardiac muscle; muscle pathology; myosin VI; sarcoplasmic reticulum; skeletal muscle; unconventional myosin