The Functional Mechanisms Of Protein HID-1 In C.elegans

Peptide hormones and neuropeptides are packaged and stored in specialized intracellular organelles called secretory granules (SGs, also known as dense core vesicles, DCVs). DCV is the specialized organelle that facilitates long-term intracellular storage of secretory proteins at high concentration. While DCVs have been known to be prominent post-Golgi carriers for almost 50 years, the exact mechanism of how DCVs maturation and its specific components recycled back to TGN remains largely unknown.In search for mutants with high-temperature-induced dauer formation (Hid) phenotype in C. elegans, a mutation in hid-1 gene was identified. The hid-1 gene encodes a novel protein with a single homolog in Drosophila melanogaster, mouse and Homo sapiens and bioinformatic analysis of HID-1 suggests no known functional domain. In addition to Hid phenotype, hid-1 mutants show pleiotropic phenotypes such as mildly uncoordinated movement (Unc), moderately resistant to the paralytic effects of aldicarb (Ric) and constipated phenotype (Aex). Here we used C. elegans as the research model to study the molecular mechanism and function of HID-1 protein.First, we introduced the functional mechanisms of DCVs, the neural circuits and molecular mechanisms underlying the sensory integration and a great animal model to study above mysteries, C. elegans.Animals integrate various environmental stimuli within the nervous system to generate proper behavioral response and plasticity. The neural circuits and molecular mechanisms underlying the sensory integration are largely unknown. Here in the second part, we identified protein HID-1 that functions in the sensory integration across modalities and associative learning in C. elegans. hid-1 mutants display defects in sensory integration between taste and olfactory signals and in two types of associative learning. We propose that HID-1 functions in neurons by regulating DCVs, which constitutes an essential component in sensory integration and behavior plasticity.In the third part, we studied HID-1, a highly conserved protein, involved in DCVs maturation and specific protein recycling thereafter. The subcellular distribution of HID-1 was localized to Golgi. Deletion of HID-1 reduced not only the number of readily releasable DCVs but also the amount of soluble peptides, but not the dense core peptides. On the contrary, the DCV-specific membrane proteins were incresed in the absence of HID-1. We propose that HID-1 participates in DCVs soluble cargo and membrane protein recycling from early endosome back to Golgi and hence affects the DCVs maturationThe last part presentsα-latrotoxin (α-LTX), a neurotoxin from black-widow spider, causes vesicles release in presynapse of nerve terminal after binding to specific membrane receptors. We found thatα-LTX inserts into the plasma membrane and forms stable non-selective cation channels, the influx of extracellular Ca2+ through the channels causes massive Ca2+-dependent exocytosis of insulin-containing vesicles. Whereas,α-LTXN4C, binding with its receptor CIRL in extracellular divalent cation-dependent way, increases [Ca2+]i by mobilization of the intracellular calcium stores.