Reference - Detail
|Author||Cai T, Fukushige T, Notkins AL, Krause M.|
|Title||Insulinoma-Associated Protein IA-2, a Vesicle Transmembrane Protein, Genetically Interacts with UNC-31/CAPS and Affects Neurosecretion in Caenorhabditis elegans.|
IA-2 (insulinoma-associated protein 2), a major autoantigen in type 1 diabetes, is a receptor-tyrosine phosphatase-like protein associated with the membrane of secretory granules of neural and endocrine-specific cells. Loss of IA-2 activity in the mouse results in reduced insulin release and additional phenotypes, consistent with a general effect on neurosecretion and hormone release. To gain further insight into the cellular mechanisms of IA-2 function, we have studied the Caenorhabditis elegans homolog, CeIA-2 encoded by the ida-1 gene. Using two independent putative null alleles of ida-1, we demonstrate that animals lacking CeIA-2 activity are viable and exhibit subtle defects. Genetic studies of mutants in ida-1 and several genes involved in neurosecretory vesicle cargo release and signaling highlight two roles for CeIA-2. First, CeIA-2 has a specific and novel genetic interaction with UNC-31/CAPS, a protein that has been shown in other systems to regulate dense-core vesicle cargo release. Second, loss of CeIA-2 activity enhances weak alleles in the insulin-like signaling pathway. These results suggest that CeIA-2 may be an important factor in dense-core vesicle cargo release with parallels to insulin signaling in mammals.
|MeSH||Aldicarb / pharmacology Alleles Animals Autoantigens Caenorhabditis elegans / drug effects Caenorhabditis elegans / physiology* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Caenorhabditis elegans Proteins / physiology* Calcium-Binding Proteins / metabolism* Drug Resistance / genetics Gene Expression Regulation / physiology Green Fluorescent Proteins Luminescent Proteins / genetics Membrane Glycoproteins / biosynthesis Membrane Glycoproteins / genetics Membrane Glycoproteins / physiology* Membrane Proteins / genetics Membrane Proteins / physiology* Motor Activity / genetics Nerve Tissue Proteins / biosynthesis Neurosecretion / genetics Neurosecretion / physiology* Phenotype Protein Tyrosine Phosphatase, Non-Receptor Type 1 Protein Tyrosine Phosphatases / genetics Protein Tyrosine Phosphatases / physiology* Receptor-Like Protein Tyrosine Phosphatases, Class 8 Recombinant Fusion Proteins / biosynthesis Recombinant Fusion Proteins / genetics Signal Transduction / genetics Signal Transduction / physiology Synaptic Transmission / genetics Synaptic Vesicles / metabolism Synaptotagmins|