| First Author | Ponomareva ON | Year | 2006 |
| Journal | Mol Cell Neurosci | Volume | 31 |
| Issue | 2 | Pages | 334-45 |
| PubMed ID | 16278083 | Mgi Jnum | J:106884 |
| Mgi Id | MGI:3619711 | Doi | 10.1016/j.mcn.2005.10.004 |
| Citation | Ponomareva ON, et al. (2006) Defective neuromuscular synaptogenesis in mice expressing constitutively active ErbB2 in skeletal muscle fibers. Mol Cell Neurosci 31(2):334-45 |
| abstractText | We overexpressed a constitutively active form of the neuregulin receptor ErbB2 (CAErbB2) in skeletal muscle fibers in vivo and in vitro by tetracycline-inducible expression. Surprisingly, CAErbB2 expression during embryonic development was lethal and impaired synaptogenesis yielding a phenotype with loss of synaptic contacts, extensive axonal sprouting, and diffuse distribution of acetylcholine receptor (AChR) transcripts, reminiscent of agrin-deficient mice. CAErbB2 expression in cultured myotubes inhibited the formation and maintenance of agrin-induced AChR clusters, suggesting a muscle- and not a nerve-origin for the defect in CAErbB2-expressing mice. Levels of tyrosine phosphorylated MuSK, the signaling component of the agrin receptor, were similar, while tyrosine phosphorylation of AChRbeta subunits was dramatically reduced in CAErbB2-expressing embryos relative to controls. Thus, a gain-of-function manipulation of ErbB2 signaling pathways renders an agrin-deficient-like phenotype that uncouples MuSK and AChR tyrosine phosphorylation. |
