TrkB Works at Postsynaptic Sites

expression of homologous truncated TrkA had no effect on the pattern of receptor clusters. Furthermore, in mutant trkB ϩ/Ϫ mice in which the level of TrkB expression The classical view of neurotrophins as target-derived is reduced, small punctate AChR regions are also ob-survival factors in the developing nervous system has served. The morphological similarity of receptor clusters changed dramatically in the last few years, perhaps due in trkB ϩ/Ϫ and truncated TrkB–overexpressing muscle to the application of improved perturbation techniques fibers is consistent with the view that TrkB-mediated and more detailed analyses of cellular phenomena. signaling is involved in the AChR clustering. Brain-derived neurotrophic factor (BDNF) and its corre-How does TrkB regulate AChR clustering at the post-sponding TrkB receptor have been found to be involved synaptic site? It is known that nerve-derived agrin is in many aspects of neural plasticity, ranging from regula-both necessary and sufficient to induce receptor cluster-tion of synaptic strength to structural plasticity of neural ing. The agrin signaling pathway has not yet been fully circuits. For example, BDNF, acting through TrkB recep-elucidated. Current wisdom is that agrin clusters and tors, can rapidly modulate synaptic transmission (Ber-activates a transmembrane protein tyrosine kinase, ninger and Poo, 1996; Black, 1999) and is also involved MuSK, which is responsible for phosphorylation of other in modifying axonal as well as dendritic morphology synaptic components including AChRs, possibly through Either chelating the endogenous TrkB ligands BDNF or in mammalian muscle, agrin-induced AChR clustering NT-4/5 or infusing excess TrkB ligands prevents the forma-requires multiple steps involving phosphorylation of tion of ocular dominance columns in mammalian primary several synaptic components. In addition, tyrosine visual cortex, a classical model of activity-dependent phosphatases are also involved in regulating the forma-synaptic plasticity (Cabelli et al., 1995, 1997). Thus, the tion of receptor clusters and the stability of preexisting TrkB-mediated signaling pathway plays diverse roles in receptor clusters (Dai and Peng, 1998). The activated synaptic patterning in the developing nervous system. TrkB receptors could directly influence AChR clustering Little is known, however, about the roles of neurotroph-by phosphorylating any of these components. Alterna-ins and the Trk receptors in the maintenance of neuronal tively, TrkB could indirectly alter the stability of preex-connections, despite the fact that they are expressed isting AChR clusters through effects on the AChR an-in many parts of the nervous system throughout life. choring proteins or components of the cytoskeleton (see Gonzalez and colleagues (1999 [this …