Dystroglycan contributes to the formation of multiple dystrophin-like complexes in brain.
In muscle, dystrophin anchors a complex of proteins at the cell surface which includes alpha-dystroglycan, beta-dystroglycan, syntrophins and dystrobrevins. Mutations in the dystrophin gene lead to muscular dystrophy and mental retardation. In contrast to muscle, little is known about the localization and the molecular interactions of dystrophin and dystrophin associated proteins (DAPs) in brain. In the present study, we show that alpha-dystroglycan and dystrophin are localized to large neurones in cerebral cortex, hippocampus, cerebellum and spinal cord. Furthermore, we show that dystroglycan is a member of three distinct dystrophin-containing complexes. Two of these complexes contain syntrophin and both dystrophin and syntrophin are enriched in post-synaptic densities. These data suggest that dystrophin and DAPs may have a role in the organization of CNS synapses. Interestingly, the enrichment for syntrophin in post-synaptic densities is not affected in mice mutant for all dystrophin isoforms. Thus in the brain, unlike in muscle, the association of syntrophin with dystrophin is not crucial for the DAP complex which suggests that it may be associated with other proteins.
Moukhles
H
H
Centre for Research in Neuroscience, McGill University and Montreal General Hospital Research Institute, Montreal, Quebec, Canada.
Carbonetto
S
S
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001923:Brain Chemistry; D002458:Cell Fractionation; D002531:Cerebellum / Q000737:chemistry / Q000166:cytology; D002540:Cerebral Cortex / Q000737:chemistry / Q000166:cytology; D003598:Cytoskeletal Proteins / Q000032:analysis* / Q000502:physiology; D049030:Dystroglycans; D016189:Dystrophin / Q000032:analysis* / Q000502:physiology; D049029:Dystrophin-Associated Proteins; D005260:Female; D051380:GRB2 Adaptor Protein; D006624:Hippocampus / Q000737:chemistry / Q000166:cytology; D015151:Immunoblotting; D007150:Immunohistochemistry; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins / Q000032:analysis* / Q000502:physiology; D008565:Membrane Proteins / Q000032:analysis; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D009124:Muscle Proteins / Q000032:analysis; D009457:Neuroglia / Q000737:chemistry* / Q000166:cytology; D009474:Neurons / Q000737:chemistry* / Q000166:cytology; D019001:Nitric Oxide Synthase / Q000032:analysis; D052248:Nitric Oxide Synthase Type I; D020033:Protein Isoforms; D011506:Proteins / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000737:chemistry / Q000166:cytology
D048868:Adaptor Proteins, Signal Transducing; D003598:Cytoskeletal Proteins; D016189:Dystrophin; D049029:Dystrophin-Associated Proteins; D051380:GRB2 Adaptor Protein; C495949:Grb2 protein, mouse; C495950:Grb2 protein, rat; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D009124:Muscle Proteins; D020033:Protein Isoforms; D011506:Proteins; C091824:syntrophin; D049030:Dystroglycans; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496321:Nos1 protein, mouse; C496322:Nos1 protein, rat