Gautam Kao1, Cecilia Nordensson2, Maria Still2, Agneta Rnnlund1, Peter Naredi2 & Simon Tuck1. C. elegans embryos that hatch in the absence of food arrest growth during the first larval stage (L1). While much has been learned about the later diapause, called dauer that worms enter on encountering adverse conditions little is known presently about the mechanisms governing L1 arrest. We have identified and characterized a gene,
asna-1, which when mutated, causes a complete but reversible arrest at the L1 stage even in the presence of food. We find that
asna-1 encodes an ATPase that functions non-autonomously to regulate larval growth.
asna-1 is expressed in a restricted set of sensory neurons and in the intestine; cells that produce insulin.
asna-1 mutants have reduced insulin signaling while overexpression of
asna-1 mimics the effects of overexpressing insulin. The human homologue ASNA1, which rescues the C. elegans mutant phenotype, is expressed at high levels in human pancreatic ?eta cells but not in other pancreatic endocrine or exocrine cell types. Increase or decrease of ASNA1 function in mouse insulinoma cells causes an increase or decrease in insulin secretion respectively. Similarly, reducing
asna-1 gene function in C. elegans causes a decrease in levels of secreted insulin. We propose that ASNA1 is a novel evolutionarily conserved modulator of insulin signaling.