title: Expression of mutant ubiquitin (UBB+1) and p62 in myotilinopathies and desminopathies.
abstract: Protein aggregates in muscle cells are the morphological hallmark of myofibrillar myopathies, including myotilinopathies and desminopathies. The aim of the present study is to analyse the expression of mutant ubiquitin (UBB+1), an aberrant form of ubiquitin which accumulates in certain disorders characterized by intracellular aggregates of proteins, and p62, a multimeric signal protein which plays an active role in aggregate formation, in muscle biopsies from patients suffering from myotilinopathy and desminopathy in order to gain understanding of the mechanisms leading to protein aggregation in these disorders. Single immunohistochemistry, and single- and double-labelling immunofluorescence and confocal microscopy for UBB+1 and p62, has been performed in muscle biopsies from patients suffering from myotilinopathy and desminopathy. Strong UBB+1 immunoreactivity, colocalizing with myotilin aggregates, was found in muscle fibres in myotilinopathies. UBB+1 accumulation, colocalizing with desmin aggregates, also occurs in desminopathies. In addition, strong p62 immunoreactivity colocalizing with myotilin aggregates was observed in myotilinopathies. Similarly, p62 immunoreactivity colocalizing with desmin aggregates was found in desminopathies. The present findings suggest that accumulation of protein aggregates in myotilinopathies and in desminopathies may be related with UBB+1/abnormal protein complexes which are resistant to proteasome degradation. Furthermore, these observations suggest a relationship between the presence of p62 and the formation of inclusions in different subtypes of myofibrillar myopathies.
authors.affiliation: Institut de Neuropatologia, Servei Anatomia Patològica, IDIBELL-Hospital Universitari de Bellvitge, Barcelona, Spain. 25169mop@comb.es
authors.forename: M
authors.initials: M
authors.lastname: Olivé
authors.forename: F W
authors.initials: FW
authors.lastname: van Leeuwen
authors.forename: A
authors.initials: A
authors.lastname: Janué
authors.forename: D
authors.initials: D
authors.lastname: Moreno
authors.forename: B
authors.initials: B
authors.lastname: Torrejón-Escribano
authors.forename: I
authors.initials: I
authors.lastname: Ferrer
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000096:biosynthesis*; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D064211:Connectin; D003598:Cytoskeletal Proteins / Q000235:genetics*; D003893:Desmin / Q000235:genetics*; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008840:Microfilament Proteins; D018613:Microscopy, Confocal; D008875:Middle Aged; D009124:Muscle Proteins / Q000235:genetics*; D009135:Muscular Diseases / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009154:Mutation; D000071456:Sequestosome-1 Protein; D025801:Ubiquitin / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D064211:Connectin; D003598:Cytoskeletal Proteins; D003893:Desmin; C577290:MYOT protein, human; D008840:Microfilament Proteins; D009124:Muscle Proteins; C099718:SQSTM1 protein, human; D000071456:Sequestosome-1 Protein; D025801:Ubiquitin