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| Defective neuromuscular synaptogenesis in agrin-deficient mutant mice |
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| Author(s): Gautam M, Noakes PG, Moscoso L, Rupp F, Scheller RH, Merlie JP, Sanes JR |
| Source: CELL Volume: 85 Issue: 4 Pages: 525-535 Published: MAY 17 1996 |
| Times Cited: 491 References: 53 |
| Abstract: During neuromuscular synapse formation, motor axons induce clustering of acetylcholine receptors (AChRs) in the muscle fiber membrane. The protein agrin, originally isolated from the basal lamina of the synaptic cleft, is synthesized and secreted by motoneurons and triggers formation of AChR clusters on cultured myotubes. We show here that postsynaptic AChR aggregates are markedly reduced in number, size, and density in muscles of agrin-deficient mutant mice. These results support the hypothesis that agrin is a critical organizer of postsynaptic differentiation. However, some postsynaptic differentiation does occur in the mutant, suggesting the existence of a second nerve-derived synaptic organizing signal. In addition, we show that intramuscular nerve branching and presynaptic differentiation are abnormal in the mutant, phenotypes which may reflect either a distinct effect of agrin or impaired retrograde signaling from a defective postsynaptic apparatus. |
| Document Type: Article |
| Language: English |
| Reprint Address: Gautam, M (reprint author), WASHINGTON UNIV, SCH MED, DEPT ANAT & NEUROBIOL, ST LOUIS, MO 63110 USA |
Addresses:
1. WASHINGTON UNIV, SCH MED, DEPT MOLEC BIOL & PHARMACOL, ST LOUIS, MO 63110 USA
2. STANFORD UNIV, SCH MED, HOWARD HUGHES MED INST, DEPT MOL & CELLULAR PHYSIOL, STANFORD, CA 94305 USA |
| Publisher: CELL PRESS, 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 |
| Subject Category: Biochemistry & Molecular Biology; Cell Biology |
| IDS Number: UM415 |
| ISSN: 0092-8674 |
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