Synaptic Specificity Is Generated by the Synaptic Guidepost Protein SYG-2 and Its Receptor, SYG-1

Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, California, United States
Cell (Impact Factor: 32.24). 04/2004; 116(6):869-81. DOI: 10.1016/S0092-8674(04)00251-X
Source: PubMed


Synaptic connections in the nervous system are directed onto specific cellular and subcellular targets. Synaptic guidepost cells in the C. elegans vulval epithelium drive synapses from the HSNL motor neuron onto adjacent target neurons and muscles. Here, we show that the transmembrane immunoglobulin superfamily protein SYG-2 is a central component of the synaptic guidepost signal. SYG-2 is expressed transiently by primary vulval epithelial cells during synapse formation. SYG-2 binds SYG-1, the receptor on HSNL, and directs SYG-1 accumulation and synapse formation to adjacent regions of HSNL. syg-1 and syg-2 mutants have defects in synaptic specificity; the HSNL neuron forms fewer synapses onto its normal targets and forms ectopic synapses onto inappropriate targets. Misexpression of SYG-2 in secondary epithelial cells causes aberrant accumulation of SYG-1 and synaptic markers in HSNL adjacent to the SYG-2-expressing cells. Our results indicate that local interactions between immunoglobulin superfamily proteins can determine specificity during synapse formation.

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    • "The nephrin and neph1 homologs syg- 2 and syg-1 appear to provide " guidepost " signals that specify the unique spatial relationship between an extending neuron and formation of a nascent synapse with its target cell[11,12]. Syg-1 and -2 mutants exhibit fewer synapses with their natural targets and form aberrant synapses with incorrect target cells presumably because the extending neurite fails to recognize its target cell for synapse formation111213. Unlike hibris and roughest that are expressed uniquely on Drosophila primary pigment cells or IOCs, mammalian nephrin and neph1 are both expressed on homologous neighboring podocytes[14]. "

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    • "IrreC/Rst and Kirre are orthologues of the C. elegans protein SYG-1, which regulates synaptogenesis of the hermaphrodite-specifi c motor neuron (HSNL) (Shen & Bargmann, 2003). The C. elegans homologue of SNS and Hbs, SYG-2, on adjacent vulva epithelial guidepost cells recruits SYG-1 in HSNL neurons to the locations in the HSNL axon where presynaptic terminals form that persist into adulthood (Shen et al., 2004). Kirre-like proteins have also been reported to occur in the vertebrate kidney (refl ected in the alternate term " Neph proteins " ), where they are required to form slit diaphragm junctions between the podocytes (Sellin et al., 2002; Ihalmo et al., 2003; Sun et al., 2003). "
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