The Narp Hypothesis?

several important questions. What roles do UNC5 ecto-McMahon (1990) has been well substantiated. Although the exact agrin-induced signaling pathway has yet to be domains play in Netrin responses, and do all Netrins within a species interact similarly with DCC and UNC5? delineated, a key effector protein is rapsyn, a peripheral membrane protein of muscle. Rapsyn can induce clus-Regulation of Netrin-mediated guidance may also result from modulatory events that serve to spatially segregate ters of the AChR upon coexpression in heterologous cells and is thought to bind directly to the AChR. Genetic UNC5 from DCC proteins in those portions of an axon's trajectory where attraction occurs. Future structure– studies in mice have demonstrated the necessary roles of agrin, MuSK, and rapsyn in synaptic differentiation function analyses of DCC and UNC5 extracellular domain associations with DCC, UNC5, Netrin, and possibly at the NMJ. Our understanding of mechanisms of receptor cluster-other families of proteins will begin to shed light on these issues. In addition, both the Bashaw and Good-ing at postsynaptic sites on central neurons has been greatly advanced in recent years by identification of man (1999) and Hong et al. (1999) studies raise crucial questions about the nature of repulsive and attractive CNS receptor binding proteins that may function in an analogous manner to rapsyn. Gephyrin binds to the in-guidance mechanisms. Might the conversion of the sign of the response to other guidance cues also employ hibitory glycine receptor ␤ subunit and is required for postsynaptic clustering of glycine receptors in spinal heteromultimeric receptor switches, such that making Semaphorins or Slits attractive is dependent upon the cord. At glutamatergic synapses, PDZ domain proteins are thought to function in receptor localization and scaf-addition or loss of unidentified receptor components? And, finally, though alteration of cyclic nucleotide levels folding to downstream signal transducing proteins (Kim and Huganir, 1999). PDZ domains of the PSD-95 family in the growth cone can convert attraction to repulsion and vice versa, does this mean that the signaling outputs bind to the C termini (-ESDV) of NMDA receptor NR2 subunits, while PDZ domains of the GRIP family and for diverse guidance cues and their equally diverse receptors converge on only one or two common signaling PICK1 bind to the C termini (-SVKI) of AMPA receptor GluR2/3 subunits. Although direct evidence is lacking pathways? Continued inwardly directed experimental reflection will undoubtedly address these questions. for a function of these PDZ domain …