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Sci. STKE, 27 July 2004
Vol. 2004, Issue 243, p. tw272
[DOI: 10.1126/stke.2432004tw272]


NEUROSCIENCE Synapse Formation by Receptor Degradation

Mutations in the RPM-1 gene in Caenorhabditis elegans cause abnormalities in the development of neuronal synapses. The RPM-1 protein contains a Ran-type guanine nucleotide exchange factor domain and multiple RING finger motifs. The latter are often found in ubiquitin E3 ligases, which suggests a role in ubiquitin-dependent regulation. Liao et al. conducted a genetic screen for genes encoding proteins that function in the same pathways as RPM-1, which yielded the fsn-1 gene. The FSN-1 protein contains an F-box domain and a SPRY domain (spla and ryanodine receptor). F-box domains are characteristic of ubiquitin ligase subunits that mediate substrate recognition, and SPRY domains also mediate protein-protein interactions. A search for proteins that physically interacted with FSN-1 turned up the receptor tyrosine kinase ALK (anaplastic lymphoma kinase). ALK is a target of ubiquitin-dependent degradation because of targeting by FSN-1; consistent with that, mutation of the alk gene rescued defects in synaptic morphology of fsn-1 mutants. Immunoprecipitation experiments provided evidence of complexes containing RPM-1, FSN-1, and other E3 ligase subunits. Such complexes appear to regulate synapse formation at least in part through control of the abundance of the ALK receptor tyrosine kinase.

E. H. Liao, W. Hung, B. Abrams, M. Zhen, An SCF-like ubiquitin ligase complex that controls presynaptic differentiation. Nature 430, 345-350 (2004). [Online Journal]

Citation: Synapse Formation by Receptor Degradation. Sci. STKE 2004, tw272 (2004).

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