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Molecular and Cellular Biology, July 2007, p. 5040-5046, Vol. 27, No. 13
0270-7306/07/$08.00+0     doi:10.1128/MCB.02228-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

GA-Binding Protein Is Dispensable for Neuromuscular Synapse Formation and Synapse-Specific Gene Expression{triangledown}

Alexander Jaworski,{dagger} Cynthia L. Smith,{ddagger} and Steven J. Burden*

Molecular Neurobiology Program, The Helen L. and Martin S. Kimmel Center for Biology and Medicine at the Skirball Institute of Biomolecular Medicine, NYU School of Medicine, 540 1st Avenue, New York, New York 10016

Received 28 November 2006/ Returned for modification 17 January 2007/ Accepted 24 April 2007

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 GABP{alpha}, the DNA-binding subunit of GABP, leads to early embryonic lethality, preventing analysis of synapse formation in gabp{alpha} mutant mice. To study the role of GABP at neuromuscular synapses, we conditionally inactivated gabp{alpha} 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 GABP{alpha}, 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.


* Corresponding author. Mailing address: 540 1st Avenue, SK 5-10, New York, NY 10016. Phone: (212) 263 7341. Fax: (212) 263 2842. E-mail: burden{at}saturn.med.nyu.edu

{triangledown} Published ahead of print on 7 May 2007.

{dagger} Present address: Tessier-Lavigne lab, Genentech Inc., South San Francisco, CA 94080.

{ddagger} Present address: Mouse Genome Informatics, The Jackson Laboratory, Bar Harbor, ME 04609-1500.


Molecular and Cellular Biology, July 2007, p. 5040-5046, Vol. 27, No. 13
0270-7306/07/$08.00+0     doi:10.1128/MCB.02228-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.




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