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-like proteins.
asna-1 mutants have reduced insulin/IGF-1 signalling (IIS) while overexpression of
asna-1 mimics the effects of overexpressing worm insulin-like proteins. The human homologue, ASNA1, which rescues the C. elegans mutant phenotype, is expressed at high levels in human pancreatic beta 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 the secreted levels of the insulin-like protein
daf-28. We propose that ASNA1 is a novel evolutionarily conserved modulator of insulin signalling.