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 of and the predicted protein unc-1 in the of of C. of protein in only the to the that a that in C. elegans. The of in the the of the of and as The of unc-24, and the first of neuronal stomatin-like proteins roles with a 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 of and the predicted protein unc-1 in the of of C. of protein in only the to the that a that in C. elegans. The of in the the of the of and as The of unc-24, and the first of neuronal stomatin-like proteins roles with a proteins stomatin-like volatile stomatin-like volatile a family of proteins that are in and chaperone with The of in The of a of C. C. and In in are C. In and protein stomatin-like C. The can be in the of The of stomatin-like to the of modification protein and the of the of with in are with and C. The family the The in or of protein with to be in protein named stomatin the of the stomatin protein in in the stomatin In a for C. that a that to be to the of stomatin and to a of with a In to the and a of stomatin protein in and A in C. the of and are the stomatin-like in Caenorhabditis elegans in the of are stomatin-like in C. elegans. stomatin-like unc-24, and are in in neuronal stomatin-like unc-1 and sensitivity to volatile stomatin with a neuronal that for The of neuronal in C. elegans to and C. The and UNC-24 to of the in in C. elegans C. In the stomatin-like unc-1 and to with the A stomatin and in stomatin and a of the of stomatin in the of the of we that of that of stomatin the of we the of in the C. elegans of that with neuronal stomatin unc-1 and the in C. we unc-1 and of and to modify sensitivity to as of neuronal stomatin we to the of stomatin-like and neuronal and and for C. elegans as and C. as and the Caenorhabditis in ssu-1(fc73) as a suppressor of unc-1 the as and with as and anesthetic as a group of a with a and the C. with enzyme of or These ssu-1(fc73) the of ssu-1(fc73) with and The with unc-1 and that ssu-1(fc73) the for and for for the the of the for the of The with the known of and the ssu-1(fc73) in the of and a of in predicted with of the phenotypic of the of to phenotypes of with unc-24, ssu-1, and in phenotype the neuronal of of unc-24, ssu-1, and unc-1 a of and unc-24, ssu-1, and unc-1 be the of of and the as the of and the of The for the and to to for the to to of the and the with that the with the the with the as The the and can the of the phenotype of the of of of uncoordinated locomotion. In the a for a the to of a of with a for a a of of of in the for to a to for with for for the three with a the of the protein protein with that the and of the the the a of the in The to and The as and of enzyme in the to the and the to the of the to the a of for to of of the with of with as a a and for with a of with and or and the a as a of the of the unc-1 disrupt of in of unc-1 sensitivity to The sensitivity the suppresses the sensitivity in a the of we of uncoordinated phenotype and suppresses the sensitivity of with the and for of the uncoordinated as of the of the the suppressor of stomatin of the suppresses the and of the neuronal ssu-1(fc73) the and of the in a of of the to in C. elegans. The in the to ssu-1(fc73) a suppressor of volatile anesthetic The in as for the the of C. elegans are The sensitivity in can be in and The and sensitivity as a of ssu-1(fc73) the volatile anesthetic of and and ssu-1(fc73) modify anesthetic a of and are of alternative developmental in C. elegans to and are of the of C. elegans In in of the developmental of to of in in a of a to the phenotype to known The to the the phenotype as the with The a of and with to that the a for neuronal ssu-1(fc73) suppresses the phenotype of that of phenotype ssu-1(fc73) and The to in the The phenotype as of the in The phenotype as of the in the of and The phenotype a of the phenotype in with as the of in the The and the of to and ssu-1(fc73) of that of a of in a small of to of to the constitutive of the ssu-1(fc73) to the or of the in a A developmental of Caenorhabditis elegans a of in a small of to of to the constitutive of the ssu-1(fc73) the of constitutive with the of in we of with to the of the The a in suppresses the phenotype of that of to with unc-24, or to play a in the developmental to and a in the to as the unc-24, and the the of the and of and unc-1 in with a in ssu-1(fc73) that for a in the predicted of of ssu-1, a the predicted and a that the the a in the predicted cytosolic the to the predicted and the the predicted are and The in ssu-1(fc73) a of the A the of the predicted protein the are to and as of and of The the of ssu-1, that protein with to cytosolic alcohol The the and of the with to the of the first with the to the with the of that ssu-1, for the to the and of provide the the the of of the of the first to of the coordinated only the the of The the phenotype The the the in anesthetic sensitivity with the for the C. with a for The in the predicted protein the to unc-1 as a or in to and of and unc-1 in with phenotype and as of the the of the protein and that protein be to a to the of the C. elegans that the only predicted C. elegans of the cytosolic of enzyme The protein and of to cytosolic alcohol in The to the to the to the and The the ssu-1(fc73) of the of enzymes a alcohol group of a of ssu-1, we proteins for the and of to the of the a of can with alternative of the first C. we predicted that the be as a modify to the of three the of the in in vitro the in be a of of the of the or a of in enzyme in in vitro of the three the to with in for of protein with of and the predicted with the of the only the the of the of in only the as the in only the the in a In of the In of to of the of The of to the and to the of the of in the In of are with of The of in the with of the The of to the the of the in C. the first phenotypic characterization of the only cytosolic alcohol in C. elegans. of neuronal sensitivity to of to cytosolic alcohol The characterization of the of and phenotypic characterization of as the of the first phenotypic characterization and of of the of The of the of the of the protein to that with alternative of the first C. the we that the of of the enzyme with are of in C. elegans in the the cytosolic alcohol in and a group the in C. elegans cytosolic cytosolic in of and small and The of sulfate can the of a cytosolic that are to The protein to the protein family of the of cytosolic alcohol that of cytosolic the and the suppressor of unc-1 and unc-24, the predicted of the of a for unc-1 and are in the of the a proteins with and with a of with the cytosolic the of in with the of UNC-1 The to of UNC-1 and UNC-24 in the to The of for the of in the or of with to the first of with The to with the of to to the phenotype of with with ssu-1(fc73) of the and linkage to a with and known These the of the phenotype to known a to with only and ssu-1(fc73) of the and to to that in phenotype of the in the C. The of with the of the as a for in the of in as a of with only that or to the a that to the of a or the The phenotype in that to in that that the of in the of and and modify The phenotype the of in the of in to In in with with the of the the of with the with in The of and the first for the of locomotion, of and the and The are in the of with the that the of the the neuronal a to and to that neuronal with to to to and deficiency or the family to the of and the small of in we the that and the are in signaling. The of to the the that of the of to to are and neuronal of of the and the protein to of as The cytosolic of with of a of to the of of and the phenotypes and of to the of the and to the and phenotypes These as the of that to the phenotypes of The of of a a predicted to the of the are to be in C. C. for the a C. The of and of a The of to and to a for in the of the in of modification of sensitivity and the of and the known and to that to sensitivity to as coordinated locomotion. of are to to the of that to to to that and to of and of of the of and in the of that the only predicted cytosolic in C. elegans a that that neuronal phenotypes are The of unc-24, and the first of neuronal roles with a A to with to The phenotype ssu-1(fc73) and can with in the These to the of phenotypes and the of the of neuronal in C. elegans. proteins stomatin-like volatile stomatin-like volatile a family of proteins that are in and chaperone with The of in The of a of C. C. and In in are C. In and protein stomatin-like C. The can be in the of The of stomatin-like to the of modification protein and the of the of with In in are with and C. The family the The in or of protein with to be in protein named stomatin the of the stomatin protein in in the stomatin In a for C. that a that to be to the of stomatin and to a of with a In to the and a of stomatin protein in and A in C. the of and are the stomatin-like in Caenorhabditis elegans in the of are stomatin-like in C. elegans. stomatin-like unc-24, and are in in neuronal stomatin-like unc-1 and sensitivity to volatile stomatin with a neuronal that for The of neuronal in C. elegans to and C. The and UNC-24 to of the in in C. elegans C. In the stomatin-like unc-1 and to with the A stomatin and in stomatin and a of the of stomatin in the of the of we that of that of stomatin the of we the of in the C. elegans of that with neuronal stomatin unc-1 and the in C. we unc-1 and of and to modify sensitivity to as of neuronal stomatin we to the of stomatin-like and neuronal and and for C. elegans as and C. as and the Caenorhabditis in ssu-1(fc73) as a suppressor of unc-1 the as and with as and anesthetic as a group of a with a and the C. with enzyme of or These ssu-1(fc73) the of ssu-1(fc73) with and The with unc-1 and that ssu-1(fc73) the for and for for the the of the for the of The with the known of and the ssu-1(fc73) in the of and a of in predicted with of the phenotypic of the of to phenotypes of with unc-24, ssu-1, and in phenotype the neuronal of of unc-24, ssu-1, and unc-1 a of and unc-24, ssu-1, and unc-1 be the of of and the as the of and the of The for the and to to for the to to of the and the with that the with the the with the as The the and can the of the phenotype of the of of of uncoordinated locomotion. In the a for a the to of a of with a for a a of of of in the for to a to for with for for the three with a the of the protein protein with that the and of the the the a of the in The to and The as and of enzyme in the to the and the to the of the to the a of for to of of the with of with as a a and for with a of with and or and the a and and for C. elegans as and C. as and the Caenorhabditis in ssu-1(fc73) as a suppressor of unc-1 the as and with as and anesthetic as a group of a with a and the C. with enzyme of or These ssu-1(fc73) the of ssu-1(fc73) with and The with unc-1 and that ssu-1(fc73) the for and for for the the of the for the of The with the known of and the ssu-1(fc73) in the of and a of in predicted with of the phenotypic of the of to phenotypes of with unc-24, ssu-1, and in phenotype the neuronal of of unc-24, ssu-1, and unc-1 a of and unc-24, ssu-1, and unc-1 be the of of and the as the of and the of The for the and to to for the to to of the and the with that the with the the with the as The the and can the of the phenotype of the of of of uncoordinated locomotion. In the a for a the to of a of with a for a a of of of in the for to a to for with for for the three with a the of the protein protein with that the and of the the the a of the in The to and The In as and of enzyme in the to the and the to the of the to the a of for to of of the with of with as a a and for with a of with and or and the a as a of the of the unc-1 disrupt of in of unc-1 sensitivity to The sensitivity the suppresses the sensitivity in a the of we of uncoordinated phenotype and suppresses the sensitivity of with the and for of the uncoordinated as of the of the the suppressor of stomatin of the suppresses the and of the neuronal ssu-1(fc73) the and of the in a of of the to in C. elegans. The in the to ssu-1(fc73) a suppressor of a of and are of alternative developmental in C. elegans to and are of the of C. elegans In in of the developmental of to of in in a of a to the phenotype to known The to the the phenotype as the with The a of and with to that the a for neuronal ssu-1(fc73) suppresses the phenotype of that of phenotype ssu-1(fc73) and The to in the The phenotype as of the in The phenotype as of the in the of and The phenotype a of the phenotype in with as the of in the The and the of to and ssu-1(fc73) of that of a of in a small of to of to the constitutive of the ssu-1(fc73) to the or of the in a A developmental of Caenorhabditis elegans a of in a small of to of to the constitutive of the ssu-1(fc73) the of constitutive with the of in we of with to the of the The a in suppresses the phenotype of that of to with unc-24, or to play a in the developmental to and a in the to as the unc-24, and the the of the and of and unc-1 in with a in ssu-1(fc73) that for a in the predicted of of ssu-1, a the predicted and a that the the a in the predicted cytosolic the to the predicted and the the predicted are and The in ssu-1(fc73) a of the A the of the predicted protein the are to and as of and of The the of ssu-1, that protein with to cytosolic alcohol The the and of the with to the of the first with the to the with the of that ssu-1, for the to the and of provide the the the of of the of the first to of the coordinated only the the of The the phenotype The the the in anesthetic sensitivity with the for the C. with a for The in the predicted protein the to unc-1 as a or in to and of and unc-1 in with phenotype and as of the the of the protein and that protein be to a to the of the C. elegans that the only predicted C. elegans of the cytosolic of enzyme The protein and of to cytosolic alcohol in The to the to the to the and The the ssu-1(fc73) of the of enzymes a alcohol group of a of ssu-1, we proteins for the and of to the of the a of can with alternative of the first C. we predicted that the be as a modify to the of three the of the in in vitro the in be a of of the of the or a of in enzyme in in vitro of the three the to with in for of protein with of and the predicted with the of the only the the of the of in only the as the in only the the in a In of the In of to of the of The of to the and to the of the of in the In of are with of The of in the with of the The of to the the of The as a of the of the unc-1 disrupt of in of unc-1 sensitivity to The sensitivity the suppresses the sensitivity in a the of we of uncoordinated phenotype and suppresses the sensitivity of with the and for of the uncoordinated as of the of the the suppressor of stomatin of the suppresses the and of the neuronal ssu-1(fc73) the and of the in a of of the to in C. elegans. The in the to ssu-1(fc73) a suppressor of a of and are of alternative developmental in C. elegans to and are of the of C. elegans In in of the developmental of to of in in a of a to the phenotype to known The to the the phenotype as the with The a of and with to that the a for neuronal ssu-1(fc73) suppresses the phenotype of that of A developmental of Caenorhabditis elegans a of in a small of to of to the constitutive of the ssu-1(fc73) the of constitutive with the of in we of with to the of the The a in suppresses the phenotype of that of to with unc-24, or to play a in the developmental to and a in the to as the unc-24, and the the of the and of and unc-1 in with a in ssu-1(fc73) that for a in the predicted of of ssu-1, a the predicted and a that the the that ssu-1, for the to the and of provide the the the of of the of the first to of the coordinated only the the of The the phenotype The the the in anesthetic sensitivity with A the for the C. with a for The in the predicted protein the to unc-1 as a or in to and of and unc-1 in with phenotype and as of the the of the protein and that protein be to a The to the of the C. elegans that the only predicted C. elegans of the cytosolic of enzyme The protein and of to cytosolic alcohol in The to the to the to the and The the ssu-1(fc73) of the of enzymes a alcohol group of a of ssu-1, we proteins for the and of to the of the a of can with alternative of the first C. we predicted that the be as a modify to the of three the of the in in vitro the in be a of of the of the or a of in enzyme in in vitro of the three the to with in for of protein with of and the predicted with the of the only the the of the of in only the as the the in C. the first phenotypic characterization of the only cytosolic alcohol in C. elegans. of neuronal sensitivity to of to cytosolic alcohol The characterization of the of and phenotypic characterization of as the of the first phenotypic characterization and of of the of The of the of the of the protein to that with alternative of the first C. the we that the of of the enzyme with are of in C. elegans in the the cytosolic alcohol in and a group the in C. elegans cytosolic cytosolic in of and small and The of sulfate can the of a cytosolic that are to The protein to the protein family of the of cytosolic alcohol that of cytosolic the and the suppressor of unc-1 and unc-24, the predicted of the of a for unc-1 and are in the of the a proteins with and with a of with the cytosolic the of in with the of UNC-1 The to of UNC-1 and UNC-24 in the to The of for the of in the or of with to the first of with The to with the of to to the phenotype of with with ssu-1(fc73) of the and linkage to a with and known These the of the phenotype to known a to with only and ssu-1(fc73) of the and to to that in phenotype of the in the C. The of with the of the as a for in the of in as a of with only that or to the a that to the of a or the The phenotype in that to in that that the of in the of and and modify The phenotype the of in the of in to In in with with the of the the of with the with in The of and the first for the of locomotion, of and the and The are in the of with the that the of the the neuronal a to and to that neuronal with to to to and deficiency or the family to the of and the small of in we the that and the are in signaling. The of to the the that of the of to to are and neuronal of of the and the protein to of as The cytosolic of with of a of to the of of and the phenotypes and of to the of the and to the and phenotypes These as the of that to the phenotypes of The of of a a predicted to the of the are to be in C. C. for the a C. The of and of a The of to and to a for in the of the in of modification of sensitivity and the of and the known and to that to sensitivity to as coordinated locomotion. of are to to the of that to to to that and to of and of of the of and in the of that the only predicted cytosolic in C. elegans a that that neuronal phenotypes are The of unc-24, and the first of neuronal roles with a A to with to The phenotype ssu-1(fc73) and can with in the These to the of phenotypes and the of the of neuronal in C. elegans. the in C. the first phenotypic characterization of the only cytosolic alcohol in C. elegans. of neuronal sensitivity to of to cytosolic alcohol The characterization of the of and phenotypic characterization of as the of the first phenotypic characterization and of of the of The of the of the of the protein to that with alternative of the first C. the we that the of of the enzyme with are of in C. elegans in the the cytosolic alcohol in and a group the in C. elegans cytosolic cytosolic in of and small and The of sulfate can the of a cytosolic that are to The protein to the protein family of the of cytosolic alcohol that of cytosolic the and the suppressor of unc-1 and unc-24, the predicted of the of a for unc-1 and are in the of the a proteins with and with a of with the cytosolic the of in with the of UNC-1 The to of UNC-1 and UNC-24 in the to The of for the of in the or of signaling. The with to the first of with The to with the of to to the phenotype of with with ssu-1(fc73) of the and linkage to a with and known These the of the phenotype to known a to with only and ssu-1(fc73) of the and to to that in phenotype of the in the C. The of with the of the as a for in the of in as a of with only that or to the a that to the of a or the The phenotype in that to in that that the of in the of and and modify The phenotype the of in the of in to In in with with the of the the of with the with in The of and the first for the of locomotion, of and the and The are in the of with the that the of the the neuronal a to and to that neuronal with to to to and deficiency or the family to the of and the small of in we the that and the are in signaling. The of to the the that of the of to to are and neuronal The of of the and the protein to of as The cytosolic of with of a of to the of of and the phenotypes and of to the of the and to the and phenotypes These as the of that to the phenotypes of The of of a a predicted to the of the are to be in C. C. for the a C. The of and of a The of to and to a for in the of the in of modification of sensitivity and the of and the known and to that to sensitivity to as coordinated locomotion. of are to to the of that to to to that and to of and of of the of and in the of In that the only predicted cytosolic in C. elegans a that that neuronal phenotypes are The of unc-24, and the first of neuronal roles with a A to with to The phenotype ssu-1(fc73) and can with in the These to the of phenotypes and the of the of neuronal in C. elegans. for for of the and for of and for with with