fukutin-related protein resides in the golgi cisternae of skeletal muscle fibres and forms disulfide-linked homodimers via an n-terminal interactionfukutin-related蛋白质存在于骨骼肌纤维的高尔基潴泡和形式disulfide-linked为通过一个氨基端交互.pdfVIP

Fukutin-Related Protein Resides in the Golgi Cisternae of Skeletal Muscle Fibres and Forms Disulfide-Linked Homodimers via an N-Terminal Interaction 1,2 2 1 1 3,4 Maisoon Alhamidi , Elisabeth Kjeldsen Buvang , Toril Fagerheim , Vigdis Brox , Sigurd Lindal , Marijke Van Ghelue1,2, Øivind Nilssen1,2* 1 Division of Child and Adolescent Health, Department of Medical Genetics, University Hospital of North-Norway, Tromsø, Norway, 2 Department of Clinical Medicine – Medical Genetics, University of Tromsø, Tromsø, Norway, 3 Department of Pathology, University Hospital of North-Norway, Tromsø, Norway, 4 Institute of Medical Biology, University of Tromsø, Tromsø, Norway Abstract Limb-Girdle Muscular Dystrophy type 2I (LGMD2I) is an inheritable autosomal, recessive disorder caused by mutations in the FuKutin-Related Protein (FKRP) gene (FKRP) located on chromosome 19 (19q13.3). Mutations in FKRP are also associated with Congenital Muscular Dystrophy (MDC1C), Walker-Warburg Syndrome (WWS) and Muscle Eye Brain disease (MEB). These four disorders share in common an incomplete/aberrant O-glycosylation of the membrane/extracellular matrix (ECM) protein a-dystroglycan. However, further knowledge on the FKRP structure and biological function is lacking, and its intracellular location is controversial. Based on immunogold electron microscopy of human skeletal muscle sections we demonstrate that FKRP co-localises with the middle-to-trans-Golgi marker MG160, between the myofibrils in human rectus femoris muscle fibres. Chemical cross-linking experiments followed by pairwise yeast 2-hybrid experiments, and co-immune precipitation, demonstrate that FKRP can exis