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Sub-cellular localisation of fukutin related protein in different cell lines and in the muscle of patients with MDC1C and LGMD2I |
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| Authors: | Torelli Silvia Brown Susan C Brockington Martin Dolatshad Nazanin F Jimenez Cecilia Skordis Leigh Feng Lucy H Merlini Luciano Jones David Hilton Romero Norma Wewer Ulla Voit Thomas Sewry Caroline A Noguchi Satoru Nishino Ichizo Muntoni Francesco |
| Affiliation: | aDubowitz Neuromuscular Unit, Department of Paediatrics, Imperial College London, Hammersmith Campus, UK bMuscle Unit, Division of Medical Genetics, Department of Experimental & Diagnostic Medicine, University of Ferrara, Via Fossato di Mortara 74, 44100 Ferrara, Italy cRadcliffe Infirmary, Oxford, UK dInstitut de Myologie, GH Pitié-Salpêtrière, 47 Boulevard de l'Hôpital 75651 Paris Cedex 13, France eInstitute of Molecular Pathology, University of Copenhagen, Denmark fDepartment of Pediatrics and Pediatric Neurology, University Hospital Essen, Germany gDepartment of Histopathology, RJAH Orthopaedic Hospital, Oswestry, UK hDepartment of Neuromuscular Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1, Ogawahigashi, Kodaira, Tokyo, Japan |
| Abstract: | MDC1C and LGMD2I are two allelic forms of muscular dystrophies caused by mutations in the gene encoding for fukutin related protein (FKRP). FKRP encodes for a putative glycosyltransferase, the precise function of which is unknown. However, the marked reduction of -dystroglycan glycosylation in the muscle of MDC1C and LGMD2I patients suggests a role for FKRP in dystroglycan processing. Using a polyclonal antibody raised against FKRP we now show that endogenous FKRP locates to the Golgi apparatus of neuronal, oligodendroglial, and the cardiac muscle cell line H9c2. In differentiated C2C12 myotubes and in transverse sections of normal skeletal and cardiac muscle, endogenous FKRP surrounded the myonuclei. This localisation was unaffected in the skeletal muscle of patients with MDC1C and LGMD2I carrying various FKRP mutations. These observations imply a specific role for FKRP during striated muscle, neuronal and glial development and suggest that protein mis-localisation is not a common mechanism of disease in FKRP-related dystrophies. |
| Keywords: | Congenital muscular dystrophy Fukutin related protein Limb girdle muscular dystrophy |
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