The Role of Autophagy in ADL-Mediated Responses in C. elegans

Abstract

Autophagy is a ubiquitous cellular degradative process crucial in times of stress and starvation. Although much is known about the mechanisms of autophagy, not much is known about how the process of autophagy is coordinated between cells and tissues in multicellular organisms. The nematode Caenorhabditis elegans is an excellent multicellular model organism to study how autophagy is regulated and coordinated in response to environmental conditions. Recent work in the lab has identified a chemoreceptor gene, srh-234, of which the expression in a single neuron (called ADL) is reduced in starved animals. Starvation is known to induce autophagy in C. elegans, and our preliminary findings suggest that mutants defective in autophagy reduce srh-234 expression, similarly as during starvation. Using these findings, we decided to investigate whether autophagy regulates this srh-234 chemoreceptor in the ADL neuron in a cellautonomous (ADL) or non-cell-autonomous manner (in a remote tissue, such as the intestine). We used a tissue-specific and RNAi enhanced method to knockdown certain autophagy genes in either the intestine or the ADL neuron, and examined srh-234 expression levels in ADL neurons. Our findings indicate that autophagy genes selectively knocked down in the intestine do not appear to alter srh-234 expression in ADL neurons, while knockdown of autophagy genes in ADL itself (i.e. atg-7, bec-1, and daf-15) results in a significant down regulation of srh-234 expression. Thus, loss of autophagy reduces the expression of srh-234 in a cell-autonomous manner, suggesting that the regulation of srh-234 and therefore ADL-mediated responses is likely not dependent on other tissues.