LDL-receptor-related protein 4 is crucial for formation of the neuromuscular junction Journal Article
| Authors: | Weatherbee, S. D.; Anderson, K. V.; Niswander, L. A. |
| Article Title: | LDL-receptor-related protein 4 is crucial for formation of the neuromuscular junction |
| Abstract: | Low-density lipoprotein receptor-related protein 4(Lrp4) is a member of a family of structurally related, single-pass transmembrane proteins that carry out a variety of functions in development and physiology, including signal transduction and receptor-mediated endocytosis. Lrp4 is expressed in multiple tissues in the mouse, and is important for the proper development and morphogenesis of limbs, ectodermal organs, lungs and kidneys. We show that Lrp4 is also expressed in the post-synaptic endplate region of muscles and is required to form neuromuscular synapses. Lrp4-mutant mice die at birth with defects in both presynaptic and postsynaptic differentiation, including aberrant motor axon growth and branching, a lack of acetylcholine receptor and postsynaptic protein clustering, and a failure to express postsynaptic genes selectively by myofiber synaptic nuclei. Our data show that Lrp4 is required during the earliest events in postsynaptic neuromuscular junction (NMJ) formation and suggest that it acts in the early, nerve-independent steps of NMJ assembly. The identification of Lrp4 as crucial factor for NMJ formation may have implications for human neuromuscular diseases such as myasthenia syndromes. |
| Keywords: | controlled study; protein expression; unclassified drug; nonhuman; protein localization; mouse; phenotype; mouse mutant; animals; mice; allele; animal tissue; mus; embryo; genetic transcription; mice, inbred c57bl; cell specificity; gene expression regulation, developmental; extremities; upregulation; ethylnitrosourea; mutagenesis; embryonic development; motoneuron; cholinergic receptor; limb development; low density lipoprotein receptor related protein; neuromuscular synapse; neuromuscular junction; nerve ending; nerve fiber growth; lrp4; lung hypoplasia; oligosyndactyly; low density lipoprotein receptor related protein 4; receptors, ldl |
| Journal Title: | Development |
| Volume: | 133 |
| Issue: | 24 |
| ISSN: | 0950-1991 |
| Publisher: | Company of Biologists |
| Date Published: | 2006-12-01 |
| Start Page: | 4993 |
| End Page: | 5000 |
| Language: | English |
| DOI: | 10.1242/dev.02696 |
| PUBMED: | 17119023 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 63" - "Export Date: 4 June 2012" - "CODEN: DEVPE" - "Source: Scopus" |
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