Dystrophin and the dystrophin-associated glycoprotein, beta-dystroglycan, co-localize in photoreceptor synaptic complexes of the human retina.
Mutations in the gene encoding for dystrophin, a membrane-associated cytoskeletal protein of muscle and several non-muscle cells, are the cause of Duchenne muscular dystrophy and Becker muscular dystrophy. Patients suffering from Duchenne muscular dystrophy have recently been shown to display an abnormal b-wave of the electroretinogram, suggesting that dystrophin is important for normal retinal transmission. In the retina, dystrophin has been localized in the outer plexiform layer where dystrophin co-localizes with postsynaptic markers of photoreceptor synaptic complexes. In the present study we addressed the question of whether two major dystrophin-associated integral membrane proteins of the muscular plasma membrane, beta-dystroglycan and adhalin, are also present in photoreceptor synaptic complexes. By double immunostaining and immunoblotting we show here that beta-dystroglycan is expressed in the human retina where it co-localizes with dystrophin in photoreceptor synaptic complexes most likely on the postsynaptic side. Adhalin was not detected in the retina. Since beta-dystroglycan is a member of a transmembrane supramolecular complex thought to be important for differentiation of the neuromuscular junction, it is an attractive hypothesis that dystroglycan (linked to dystrophin) might also play a similar role in differentiation of the photoreceptor synapse. A further outcome of this study is that beta-dystroglycan is not only present in the neuromuscular junction but also associated with a well-defined synaptic complex of the central nervous system. These findings indicate a more general role of this dystrophin-associated membrane protein in synaptic functions.
Drenckhahn
D
D
Institute of Anatomy, University of Würzburg, Germany.
Holbach
M
M
Ness
W
W
Schmitz
F
F
Anderson
L V
LV
D000328:Adult; D000368:Aged; D003598:Cytoskeletal Proteins / Q000032:analysis*; D049030:Dystroglycans; D016189:Dystrophin / Q000032:analysis*; D005134:Eye Neoplasms / Q000473:pathology; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D008297:Male; D008545:Melanoma / Q000473:pathology; D008562:Membrane Glycoproteins / Q000032:analysis*; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000166:cytology / Q000473:pathology; D009136:Muscular Dystrophies; D010786:Photoreceptor Cells / Q000166:cytology* / Q000473:pathology*; D012016:Reference Values; D017948:Retinal Rod Photoreceptor Cells / Q000166:cytology / Q000473:pathology; D049031:Sarcoglycans; D013569:Synapses / Q000473:pathology* / Q000648:ultrastructure*
D003598:Cytoskeletal Proteins; C483081:DAG1 protein, human; D016189:Dystrophin; D008562:Membrane Glycoproteins; D049031:Sarcoglycans; D049030:Dystroglycans