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Nuclear localization of valosin‐containing protein in normal muscle and muscle affected by inclusion‐body myositis
Author(s) -
Greenberg Steven A.,
Watts Giles D.,
Kimonis Virginia E.,
Amato Anthony A.,
Pinkus Jack L.
Publication year - 2007
Publication title -
muscle and nerve
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.025
H-Index - 145
eISSN - 1097-4598
pISSN - 0148-639X
DOI - 10.1002/mus.20823
Subject(s) - inclusion body myositis , myositis , muscle protein , medicine , chemistry , anatomy , skeletal muscle
Inclusion‐body myopathy with Paget's disease and frontotemporal dementia (IBMPFD) is a disease of muscle, bone, and brain that results from mutations in the gene encoding valosin‐containing protein (VCP). The mechanism of disease resulting from VCP mutations is unknown. Previous studies of VCP localization in normal human muscle samples have found a capillary and perinuclear distribution, but not a nuclear localization. Here we demonstrate that VCP is present in both myonuclei and endothelial cell nuclei in normal human muscle tissue. The immunodetection of VCP varies with acetone or paraformaldehyde fixation. Within the nucleus, VCP associates with the nucleolar protein fibrillarin and Werner syndrome protein (Wrnp) in normal and IBMPFD muscle. In patients with inclusion‐body myositis (IBM), normal nuclear localization is present and some rimmed vacuoles are lined with VCP. These findings suggest that impairment in the nuclear function of VCP might contribute to the muscle pathology occurring in IBMPFD. Muscle Nerve, 2007