Analysis of differential gene expression profiles in Caenorhabditis elegans knockouts for the v-SNARE master protein 1.

At chemical synapses, neurons communicate information to other cells by secreting neurotransmitters or neuropeptides into the synaptic cleft, which then bind to receptors on the target cell. Preliminary work performed in our laboratory has shown that mutant nematodes lacking a protein called VSM-1 have increased synaptic density compared with the wild type. Consequently, we hypothesized that genes expressed in vsm-1 mutants mediate enhanced synaptogenesis.

Lanthionine ketimine ethyl ester partially rescues neurodevelopmental defects in unc-33 (DPYSL2/CRMP2) mutants.

Lanthionine ketimine (LK) is a natural sulfur amino acid metabolite with potent neurotrophic activity. Proteomics indicate that LK interacts with collapsin response mediator protein-2 (CRMP2/DPYSL2/UNC-33), a brain-enriched protein that was shown to regulate cytoskeletal remodeling, neuronal morphology, and synaptic function. To elucidate further the molecular interplay and biological action of LK and UNC-33, we began examining the nervous system of Caenorhabditis elegans nematodes in which both LK concentrations and UNC-33 protein were manipulated.

Determining genetic expression profiles in C. elegans using microarray and real-time PCR.

Synapses are composed of a presynaptic active zone in the signaling cell and a postsynaptic terminal in the target cell. In the case of chemical synapses, messages are carried by neurotransmitters released from presynaptic terminals and received by receptors on postsynaptic cells. Our previous research in Caenorhabditis elegans has shown that VSM-1 negatively regulates exocytosis.

Tomosyn inhibits synaptic vesicle priming in Caenorhabditis elegans.

Caenorhabditis elegans TOM-1 is orthologous to vertebrate tomosyn, a cytosolic syntaxin-binding protein implicated in the modulation of both constitutive and regulated exocytosis. To investigate how TOM-1 regulates exocytosis of synaptic vesicles in vivo, we analyzed C. elegans tom-1 mutants.