title: GA-binding protein is dispensable for neuromuscular synapse formation and synapse-specific gene expression.
abstract: The mRNAs encoding postsynaptic components at the neuromuscular junction are concentrated in the synaptic region of muscle fibers. Accumulation of these RNAs in the synaptic region is mediated, at least in part, by selective transcription of the corresponding genes in synaptic myofiber nuclei. The transcriptional mechanisms that are responsible for synapse-specific gene expression are largely unknown, but an Ets site in the promoter regions of acetylcholine receptor (AChR) subunit genes and other "synaptic" genes is required for synapse-specific transcription. The Ets domain transcription factor GA-binding protein (GABP) has been implicated to mediate synapse-specific gene expression. Inactivation of GABPalpha, the DNA-binding subunit of GABP, leads to early embryonic lethality, preventing analysis of synapse formation in gabpalpha mutant mice. To study the role of GABP at neuromuscular synapses, we conditionally inactivated gabpalpha in skeletal muscle and studied synaptic differentiation and muscle gene expression. Although expression of rb, a target of GABP, is elevated in muscle tissue deficient in GABPalpha, clustering of synaptic AChRs at synapses and synapse-specific gene expression are normal in these mice. These data indicate that GABP is dispensable for synapse-specific transcription and maintenance of normal AChR expression at synapses.
authors.affiliation: The Helen L. and Martin S. Kimmel Center for Biology and Medicine, Skirball Institute of Biomoledular Medicine, NYU School of Medicine, New York, NY 10016, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Jaworski
authors.forename: Cynthia L
authors.initials: CL
authors.lastname: Smith
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Burden
mesh_terms: D000483:Alleles; D000818:Animals; D000831:Animals, Newborn; D047108:Embryonic Development; D051268:GA-Binding Protein Transcription Factor / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D018390:Gene Targeting; D051379:Mice; D018482:Muscle, Skeletal / Q000378:metabolism; D050505:Mutant Proteins / Q000378:metabolism; D009469:Neuromuscular Junction / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011950:Receptors, Cholinergic / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000235:genetics
chemical_list: D051268:GA-Binding Protein Transcription Factor; C495656:Gabpa protein, mouse; D050505:Mutant Proteins; D012333:RNA, Messenger; D011950:Receptors, Cholinergic; D016160:Retinoblastoma Protein