Sulfated Signal from ASJ Sensory Neurons Modulates Stomatin-dependent Coordination in Caenorhabditis elegans

Abstract

The neuronal stomatin-like proteins UNC-1 and UNC-24 play important roles in the nervous system of Caenorhabditis elegans. These neuronal stomatin-like proteins are putative chaperone proteins that can modify volatile anesthetic sensitivity and disrupt coordinated locomotion. A suppressor of unc-1 and unc-24, named ssu-1(fc73) (for suppressor of stomatin uncoordination), suppresses three phenotypes of neuronal stomatin-like protein deficiency as follows: volatile anesthetic sensitivity, uncoordinated locomotion, and a constitutive alternative developmental phenotype known as dauer. Here we provide the first phenotypic characterization of ssu-1, predicted to be the only C. elegans cytosolic alcohol sulfotransferase, a family of enzymes that catalyze a sulfate linkage with the alcohol group of small molecules for the purposes of detoxification or modification of signaling. In vitro enzyme analysis of bacterially expressed SSU-1 demonstrates sulfotransferase activity and thus confirms the function predicted by protein sequence similarities. Whereas unc-1 is expressed in the majority of neurons of C. elegans, expression of SSU-1 protein in only the two ASJ amphid interneurons is sufficient to restore the wild type phenotype. This work demonstrates that SSU-1 is a functional sulfotransferase that likely modifies endocrine signaling in C. elegans. The expression of SSU-1 in the ASJ neurons refines the understanding of the function of these cells and supports their classification as endocrine tissue. The relationship of unc-1, unc-24, and ssu-1 is the first association of neuronal stomatin-like proteins sharing regulatory roles with a sulfotransferase enzyme.

Cis- and Trans-Regulatory Mechanisms of Gene Expression in the ASJ Sensory Neuron of Caenorhabditis elegans

“…To date, only the genes trx-1 (thioredoxin-1) and ssu-1 (alcohol sulfotransferase-1) have been reported to be expressed exclusively in ASJ neurons (Carroll et al 2006;MirandaVizuete et al 2006). TRX-1 belongs to the thioredoxin family of redox proteins, playing a role in regulating worm longevity and dauer formation (Miranda-Vizuete et al 2006;FierroGonzalez et al 2011a,b).…”

The PAPS transporter PST-1 is required for heparan sulfation and is essential for viability and neural development inC. elegans

“…S3). This gene might be required in C. elegans for the biosynthesis of a secreted compound(s) involved in dauer formation and locomotion (Carroll et al, 2006). We also identified at least five genes with similarity to genes encoding heparan sulfate (HS) sulfotransferases in the C. elegans genome.…”

“…Numerous essential genes have been identified on the left arm of chromosome V, and grouped into complementation groups by deficiency mapping and complementation tests (Johnsen and Baillie, 1991;Stewart et al, 1991). Using the cold-sensitive lethality, we (Carroll et al, 2006) Genes were identified by keyword search in GenBank, PFAM and re-iterative BLAST searches.…”

Sulfation and related genes in Caenorhabditis elegans

“…The gene is highly expressed in embryos, growing larvae and in dauer larvae. Expression of SSU-1 in the ASJ neurons (amphid sensory neurons) was demonstrated and the protein showed sulfotransferase activity in vitro (28). This protein may modify endocrine signals in the worm.…”