A Novel Conserved Gene that Might Be Involved in Synaptic Vesicle Release. Export

@inproceedings{citeulike:3333287, abstract = { To identify mutants that perceive a constitutive state of food deprivation, we screened for mutants that behave as if they had been food-deprived when well fed. Well-fed C. elegans that encounter a bacterial lawn slow their locomotion, exhibiting the basal-slowing response. Acutely food-deprived animals slow more upon entering a bacterial lawn, exhibiting the enhanced-slowing response. Using a mod-5 deletion background, we screened for mutants that exhibited enhanced slowing in the well-fed state; deletion of mod-5, which encodes a serotonin reuptake transporter, provided a sensitized strain background facilitating the recovery of mutants. We isolated 17 mutants that were restored to normal locomotion on food by methiothepin, a serotonin-gated receptor antagonist, suggesting that the mutations affect serotonin signaling and the ability to modulate behavior in response to past feeding experience. Two of the 17 mutants, n4022 and n3925, failed to complement each other and mapped to a 50 kb region on LG III. We identified a single gene, C44B9.1, capable of rescuing the locomotion defects of n4022. We identified in the n4022 and n3925 strains single point mutations in C44B9.1 predicted to result in premature stop codons. The protein encoded by C44B9.1 has no conserved domains of known function but is significantly similar to uncharacterized proteins found in other organisms, including humans (29\% identical, 49\% similar). Expression of a C44B9.1 cDNA using a pan-neuronal promoter (unc-119), but not a body-wall muscle promoter (myo-3), rescued the locomotion and Hid defects (see below) of n4022 animals. Using a transcriptional gfp reporter driven by a C44B9.1 promoter, we observed expression in several head neurons, the identities of which we have not yet confirmed. The n4022 strain has a decreased sensitivity to aldicarb, an acetylcholinesterase inhibitor, and an increased sensitivity to levamisole, an acetylcholine receptor agonist, suggesting that the n4022 defect may act presynaptically. The drug-sensitivity profile of n4022 is similar to that of strains mutant for any one of several conserved genes implicated in the regulation of vesicle exocytosis (unc-64, unc-31, hid-1, and aex-3). Similar to mutations in this group of genes, n4022 also causes high-temperature (27C) induced dauer (Hid) formation on its own and dauer formation at 25C in combination with unc-31(e928) or unc-64(e246).}, author = {Froehlich, Allan and Horvitz, Bob}, citeulike-article-id = {3333287}, citeulike-linkout-0 = {http://www.wormbase.org/db/misc/paper?name=WBPaper00030366}, journal = {International Worm Meeting}, keywords = {c\_elegans, caenorhabditis\_elegans, celegans, elegans, f56a87, hid-1, k02e102, k12f21, m1421, meeting\_abstract, mod-5, myo-3, nematode, unc-119, unc-31, unc-64, wormbase, y54e10br7, zk8971}, posted-at = {2008-09-24 18:52:07}, priority = {3}, title = {A Novel Conserved Gene that Might Be Involved in Synaptic Vesicle Release.}, url = {http://www.wormbase.org/db/misc/paper?name=WBPaper00030366}, year = {2007} }

TY - CONF ID - citeulike:3333287 L3 - citeulike-article-id:3333287 N2 - To identify mutants that perceive a constitutive state of food deprivation, we screened for mutants that behave as if they had been food-deprived when well fed. Well-fed C. elegans that encounter a bacterial lawn slow their locomotion, exhibiting the basal-slowing response. Acutely food-deprived animals slow more upon entering a bacterial lawn, exhibiting the enhanced-slowing response. Using a mod-5 deletion background, we screened for mutants that exhibited enhanced slowing in the well-fed state; deletion of mod-5, which encodes a serotonin reuptake transporter, provided a sensitized strain background facilitating the recovery of mutants. We isolated 17 mutants that were restored to normal locomotion on food by methiothepin, a serotonin-gated receptor antagonist, suggesting that the mutations affect serotonin signaling and the ability to modulate behavior in response to past feeding experience. Two of the 17 mutants, n4022 and n3925, failed to complement each other and mapped to a 50 kb region on LG III. We identified a single gene, C44B9.1, capable of rescuing the locomotion defects of n4022. We identified in the n4022 and n3925 strains single point mutations in C44B9.1 predicted to result in premature stop codons. The protein encoded by C44B9.1 has no conserved domains of known function but is significantly similar to uncharacterized proteins found in other organisms, including humans (29% identical, 49% similar). Expression of a C44B9.1 cDNA using a pan-neuronal promoter (unc-119), but not a body-wall muscle promoter (myo-3), rescued the locomotion and Hid defects (see below) of n4022 animals. Using a transcriptional gfp reporter driven by a C44B9.1 promoter, we observed expression in several head neurons, the identities of which we have not yet confirmed. The n4022 strain has a decreased sensitivity to aldicarb, an acetylcholinesterase inhibitor, and an increased sensitivity to levamisole, an acetylcholine receptor agonist, suggesting that the n4022 defect may act presynaptically. The drug-sensitivity profile of n4022 is similar to that of strains mutant for any one of several conserved genes implicated in the regulation of vesicle exocytosis (unc-64, unc-31, hid-1, and aex-3). Similar to mutations in this group of genes, n4022 also causes high-temperature (27C) induced dauer (Hid) formation on its own and dauer formation at 25C in combination with unc-31(e928) or unc-64(e246). JF - International Worm Meeting TI - A Novel Conserved Gene that Might Be Involved in Synaptic Vesicle Release. KW - c_elegans KW - caenorhabditis_elegans KW - celegans KW - elegans KW - f56a87 KW - hid-1 KW - k02e102 KW - k12f21 KW - m1421 KW - meeting_abstract KW - mod-5 KW - myo-3 KW - nematode KW - unc-119 KW - unc-31 KW - unc-64 KW - wormbase KW - y54e10br7 KW - zk8971 AU - Froehlich, Allan AU - Horvitz, Bob PY - 2007/// UR - http://www.wormbase.org/db/misc/paper?name=WBPaper00030366 ER -