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,nerveindependent steps of NMJ assembly. The identification of Lrp4 as a crucial factor for NMJ formation may have implications for human neuromuscular diseases such as myasthenia syndromes.
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The perinatal lethality of Lrp4-deficient mice prevented effective study of Lrp4 in the central nervous system until recently.
“which has precluded effective study of the role of Lrp4 in the CNS until recently [92]”
From ApoE, ApoE Receptors, and the Synapse in Alzheimer's Disease (2017) · cites this paper as [92]
Mice completely lacking Lrp4 die around birth.
“mice that are completely deficient in Lrp4 die perinatally”
From ApoE, ApoE Receptors, and the Synapse in Alzheimer's Disease (2017) · cites this paper as [92]
Lrp4 is absolutely required for neuromuscular junction development in mice.
“the absolute requirement of Lrp4 for NMJ development in mice”
From ApoE, ApoE Receptors, and the Synapse in Alzheimer's Disease (2017) · cites this paper as [92]
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- Authors
- Weatherbee, S. D., Anderson, K. V., & Niswander, L. A.
- Affiliations
- Howard Hughes Medical Institute (US)
- Developmental Biology Program, Sloan-Kettering Institute, New York, NY 10021,USA.
- Venue
- Development
- Publisher
- The Company of Biologists
- Published
- 2006-12-15
- Volume
- 133
- Issue
- 24
- Pages
- 4993-5000
- ISSN
- 0950-1991 (ISSN-L)
- 1477-9129
- OpenAlex
- W2144696840
- Cited by
- 351
- References
- 71
- Citations by year
- 2026: 9 · 2025: 18 · 2024: 14 · 2023: 16 · 2022: 15 · 2021: 17 · 2020: 25 · 2019: 23 · 2018: 25 · 2017: 15 · 2016: 16 · 2015: 15 · 2014: 17 · 2013: 29 · 2012: 27
- FWCI
- 7.89
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Development (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD032427, R01HD32427, U01 HD43478, U01HD043478)
- Topics
- Health Sciences › Medicine › Neurology › Myasthenia Gravis and Thymoma
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Keywords
- LRP4, neuromuscular junction formation, postsynaptic differentiation, acetylcholine receptor clustering, myasthenia
- MeSH terms
- Animals, Extremities, Mice, Inbred C57BL, Neuromuscular Junction, Phenotype, Receptors, LDL, Mutagenesis, Gene Expression Regulation, Developmental, LDL-Receptor Related Proteins, Embryonic Development, Mice
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