ASNA-1 positively regulates insulin secretion in C. elegans and mammalian cells.
C. elegans worms hatching in the absence of food show growth arrest during the first larval stage (L1). While much has been learned about the later diapause, dauer, which worms enter under adverse conditions, much less is known about the mechanisms governing L1 arrest. Here we show that worms lacking activity of the asna-1 gene arrest growth reversibly at the L1 stage even when food is abundant. asna-1 encodes an ATPase that functions nonautonomously to regulate growth. asna-1 is expressed in a restricted set of sensory neurons and in insulin-producing intestinal cells. asna-1 mutants are reduced in insulin secretion while overexpression of asna-1 mimics the effects of insulin overexpression. Human ASNA1 is highly expressed in pancreatic beta cells, but not in other pancreatic endocrine cell types, and regulates insulin secretion in cultured cells. We propose that ASNA1 is an evolutionarily conserved modulator of insulin signaling.
Kao
Gautam
G
Umeå Center for Molecular Pathogenesis, Umeå University, SE-901 87 Umeå, Sweden.
Nordenson
Cecilia
C
Still
Maria
M
Rönnlund
Agneta
A
Tuck
Simon
S
Naredi
Peter
P
D000818:Animals; D053501:Arsenite Transporting ATPases / Q000378:metabolism*; D017173:Caenorhabditis elegans / Q000254:growth & development / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D007340:Insulinoma / Q000378:metabolism; D061385:Insulins; D007814:Larva / Q000254:growth & development; D009154:Mutation; D010641:Phenotype; D011972:Receptor, Insulin / Q000378:metabolism; D015398:Signal Transduction
D029742:Caenorhabditis elegans Proteins; C489667:GET3 protein, human; D007328:Insulin; D061385:Insulins; C473608:daf-28 protein, C elegans; D011972:Receptor, Insulin; C518267:ASNA-1 protein, C elegans; D053501:Arsenite Transporting ATPases; C506972:Asna1 protein, mouse