A novel mechanism for modulating synaptic gene expression: differential localization of alpha-dystrobrevin transcripts in skeletal muscle.
Alpha-dystrobrevin is a dystrophin-related and -associated protein that is involved in synapse maturation and is required for normal muscle function. There are three protein isoforms in skeletal muscle, alpha-dystrobrevin-1, -2, and -3 that are encoded by the single alpha-dystrobrevin gene. To understand the role of these proteins in muscle we have investigated the localisation and transcript distribution of the different alpha-dystrobrevin isoforms. Alpha-dystrobrevin-1 and -2 are concentrated at the neuromuscular junction and are both recruited into agrin-induced acetylcholine receptor clusters in cultured myotubes. We also demonstrate that all alpha-dystrobrevin mRNAs are transcribed from a single promoter in skeletal muscle. However, only transcripts encoding alpha-dystrobrevin-1 are preferentially accumulated at postsynaptic sites. These data suggest that the synaptic accumulation of alpha-dystrobrevin-1 mRNA occurs posttranscriptionally, identifying a novel mechanism for synaptic gene expression. Taken together, these results indicate that different isoforms possess distinct roles in synapse formation and possibly in the pathogenesis of muscular dystrophy.
Newey
S E
SE
Department of Human Anatomy and Genetics, MRC Functional Genetics Unit, University of Oxford, South Parks Road, Oxford, OX1 3QX, United Kingdom.
Gramolini
A O
AO
Wu
J
J
Holzfeind
P
P
Jasmin
B J
BJ
Davies
K E
KE
Blake
D J
DJ
D018171:Agrin / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D049029:Dystrophin-Associated Proteins; D005786:Gene Expression Regulation / Q000502:physiology*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D018482:Muscle, Skeletal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D011940:Receptor Aggregation / Q000187:drug effects; D011950:Receptors, Cholinergic / Q000187:drug effects / Q000378:metabolism; D013569:Synapses / Q000235:genetics / Q000378:metabolism*
D018171:Agrin; D003598:Cytoskeletal Proteins; D049029:Dystrophin-Associated Proteins; D008565:Membrane Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger; D011950:Receptors, Cholinergic; C098885:dystrobrevin