Kao Gautam, Nordenson Cecilia, Still Maria, Rönnlund Agneta, Tuck Simon, Naredi Peter
Umeå Center for Molecular Pathogenesis, Umeå University, SE-901 87 Umeå, Sweden.
Cell. 2007 Feb 9;128(3):577-87. doi: 10.1016/j.cell.2006.12.031.
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.
在没有食物的情况下孵化出的秀丽隐杆线虫在第一个幼虫阶段（L1）会出现生长停滞。虽然我们已经对后期的滞育（即线虫在不利条件下进入的 dauer 状态）有了很多了解，但对于控制 L1 停滞的机制却知之甚少。在这里，我们表明，即使食物充足，缺乏 asna - 1 基因活性的线虫在 L1 阶段也会可逆地停止生长。asna - 1 编码一种 ATP 酶，其功能是非自主性地调节生长。asna - 1 在一组特定的感觉神经元和产生胰岛素的肠细胞中表达。asna - 1 突变体的胰岛素分泌减少，而 asna - 1 的过表达模拟了胰岛素过表达的效果。人类 ASNA1 在胰腺β细胞中高度表达，但在其他胰腺内分泌细胞类型中不表达，并在培养细胞中调节胰岛素分泌。我们提出 ASNA1 是胰岛素信号传导的一种进化保守调节因子。
