Regulation of MuSK expression by a novel signaling pathway.
MuSK is a receptor tyrosine kinase essential for neuromuscular junction formation. Expression of the MuSK gene is tightly regulated during development and at the neuromuscular junction. However, little is known about molecular mechanisms regulating its gene expression. Here we report a characterization of the promoter of the mouse MuSK gene. The transcription of MuSK starts at multiple sites with a major site 51 nt upstream of the translation start site. We have identified an E-box-like cis-element that is both required and sufficient for differentiation-dependent transcription. Interestingly, the promoter activity of the MuSK gene did not respond to neuregulin, a factor believed to mediate the synapse-specific transcription of acetylcholine receptor subunit genes. Rather, MuSK expression is increased in muscle cells stimulated with Wnt or at conditions when the Wnt signaling was activated. These results suggest a novel mechanism for the MuSK synapse-specific expression.
Kim
Chang-Hoon
CH
Department of Neurobiology, University of Alabama at Birmingham, Civitan International Research Center, 35294, USA.
Xiong
Wen C
WC
Mei
Lin
L
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D019556:COS Cells; D002454:Cell Differentiation; D002460:Cell Line; D003001:Cloning, Molecular; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D009132:Muscles / Q000166:cytology; D020880:Neuregulins / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000096:biosynthesis* / Q000235:genetics*; D011950:Receptors, Cholinergic / Q000096:biosynthesis* / Q000235:genetics*; D012260:Ribonucleases / Q000378:metabolism; D015398:Signal Transduction; D013569:Synapses / Q000378:metabolism; D014018:Tissue Distribution; D014158:Transcription, Genetic; D014162:Transfection; D019076:Transgenes; D051153:Wnt Proteins; D029961:Zebrafish Proteins
D020880:Neuregulins; D011518:Proto-Oncogene Proteins; D011950:Receptors, Cholinergic; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D008156:Luciferases; C095714:MUSK protein, human; D020794:Receptor Protein-Tyrosine Kinases; D012260:Ribonucleases