Neurotrophins regulate agrin-induced postsynaptic differentiation

• DOI: 10.1073/pnas.96.3.1112
• Publication Date: 2002-07-26T14:42:40Z
• Authors: David G. Wells; Beth A. McKechnie; Samir Kelkar; Justin R. Fallon
• Keywords: Agrin

The precise orchestration of synaptic differentiation is critical for efficient information exchange in the nervous system. nerve–muscle synapse forms response to agrin, which secreted from motor nerve terminal and induces clustering acetylcholine receptors (AChRs) other elements postsynaptic apparatus on subjacent muscle cell surface. In view highly restricted spatial localization plasticity neuromuscular junctions, it seems likely that formation maintenance are regulated by additional, as-yet-unidentified factors. Here, we tested whether neurotrophins modulate agrin-induced specializations. We show both brain-derived neurotrophic factor (BDNF) neurotrophin-4 (NT-4) inhibit AChR cultured myotubes. Nerve growth NT-3 without effect. Muscle cells express full-length TrkB, cognate receptor BDNF NT-4. Direct activation this anti-TrkB antibodies mimicked BDNF/NT-4 inhibition clustering. This be an intrinsic mechanism regulating clustering, because neutralization endogenous TrkB ligands resulted elevated levels even absence added agrin. Finally, high concentrations agrin can occlude These results indicate interplay between regulate They also suggest a suppression specializations at nonjunctional regions.