Article

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

Howard Hughes Medical Institute, Department of Anatomy, The University of California, San Francisco, San Francisco, CA 94143, USA.
Cell (Impact Factor: 33.12). 04/2004; 116(6):869-81. DOI: 10.1016/S0092-8674(04)00251-X
Source: PubMed

ABSTRACT 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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    • "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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    • "For this purpose, we used syg-1;syg-2 double-mutant animals and coinjected them with chimeric syg-1 and chimeric syg-2 under the unc-86 and egl-17 promoters, respectively. The egl- 17 promoter drives expression in the secondary vulva epithelial cells, and expression of syg-2 with this promoter has been shown to reconstitute synapses in an axonal fragment contacting these cells (Figures 6A–6D) (Shen et al., 2004). We observed that chimeras with Drosophila and mouse D1s can rescue the syg-1;syg-2 phenotype (Figures 6E and 6F). "
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