Alternatively spliced isoforms of nerve- and muscle-derived agrin: their roles at the neuromuscular junction
- PMID: 10402191
- DOI: 10.1016/s0896-6273(00)80751-5
Alternatively spliced isoforms of nerve- and muscle-derived agrin: their roles at the neuromuscular junction
Abstract
Agrin induces synaptic differentiation at the skeletal neuromuscular junction (NMJ); both pre- and postsynaptic differentiation are drastically impaired in its absence. Multiple alternatively spliced forms of agrin that differ in binding characteristics and bioactivity are synthesized by nerve and muscle cells. We used surgical chimeras, isoform-specific mutant mice, and nerve-muscle cocultures to determine the origins and nature of the agrin required for synaptogenesis. We show that agrin containing Z exons (Z+) is a critical nerve-derived inducer of postsynaptic differentiation, whereas neural isoforms containing a heparin binding site (Y+) and all muscle-derived isoforms are dispensable for major steps in synaptogenesis. Our results also suggest that the requirement of agrin for presynaptic differentiation is mediated indirectly by its ability to promote postsynaptic production or localization of appropriate retrograde signals.
Similar articles
-
Overexpression of agrin isoforms in Xenopus embryos alters the distribution of synaptic acetylcholine receptors during development of the neuromuscular junction.Dev Biol. 1999 Jan 1;205(1):22-32. doi: 10.1006/dbio.1998.9104. Dev Biol. 1999. PMID: 9882495
-
The MuSK activator agrin has a separate role essential for postnatal maintenance of neuromuscular synapses.Proc Natl Acad Sci U S A. 2014 Nov 18;111(46):16556-61. doi: 10.1073/pnas.1408409111. Epub 2014 Nov 3. Proc Natl Acad Sci U S A. 2014. PMID: 25368159 Free PMC article.
-
New insights into the roles of agrin.Nat Rev Mol Cell Biol. 2003 Apr;4(4):295-308. doi: 10.1038/nrm1074. Nat Rev Mol Cell Biol. 2003. PMID: 12671652 Review.
-
Defective neuromuscular synaptogenesis in agrin-deficient mutant mice.Cell. 1996 May 17;85(4):525-35. doi: 10.1016/s0092-8674(00)81253-2. Cell. 1996. PMID: 8653788
-
Agrin orchestrates synaptic differentiation at the vertebrate neuromuscular junction.Trends Neurosci. 1998 Jan;21(1):22-7. doi: 10.1016/s0166-2236(97)01154-5. Trends Neurosci. 1998. PMID: 9464682 Review.
Cited by
-
A conserved RNA switch for acetylcholine receptor clustering at neuromuscular junctions in chordates.bioRxiv [Preprint]. 2024 Jul 6:2024.07.05.602308. doi: 10.1101/2024.07.05.602308. bioRxiv. 2024. PMID: 39005407 Free PMC article. Preprint.
-
The impact of alternative splicing in vivo: mouse models show the way.RNA. 2007 Aug;13(8):1155-71. doi: 10.1261/rna.554607. Epub 2007 Jun 11. RNA. 2007. PMID: 17563071 Free PMC article. Review.
-
A genetic model for a central (septum transversum) congenital diaphragmatic hernia in mice lacking Slit3.Proc Natl Acad Sci U S A. 2003 Apr 29;100(9):5217-22. doi: 10.1073/pnas.0730709100. Epub 2003 Apr 17. Proc Natl Acad Sci U S A. 2003. PMID: 12702769 Free PMC article.
-
Nerve, Muscle, and Synaptogenesis.Cells. 2019 Nov 16;8(11):1448. doi: 10.3390/cells8111448. Cells. 2019. PMID: 31744142 Free PMC article. Review.
-
Muscle-Specific Cellular and Molecular Adaptations to Late-Life Voluntary Concurrent Exercise.Function (Oxf). 2022 May 23;3(4):zqac027. doi: 10.1093/function/zqac027. eCollection 2022. Function (Oxf). 2022. PMID: 35774589 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases