SER-7, a Caenorhabditis elegans 5-HT7-like receptor, is essential for the 5-HT stimulation of pharyngeal pumping and egg laying
SER-7, a Caenorhabditis elegans 5-HT7-like receptor, is essential for the 5-HT stimulation of pharyngeal pumping and egg laying
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DOI：
10.1534/genetics.105.044495
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发表时间：
2006-01-01
期刊：
影响因子：
3.3
通讯作者：
Komuniecki, RW
中科院分区：
文献类型：
--
作者：
Hobson, RJ;Hapiak, VM;Komuniecki, RW
5-羟色胺（5-HT）刺激秀丽隐杆线虫的咽泵和产卵。四种不同的5-HT受体已被部分表征，但对它们在体内的功能知之甚少。SER-7与哺乳动物5-HT 7受体具有最大的序列同一性，并且当在COS-7细胞中表达时，与腺苷酸环化酶的刺激偶联。然而，许多5-HT 7特异性激动剂对SER-7具有低亲和力。5-HT不能刺激咽泵和发射的MC运动神经元在动物含有推定的ser-7（tm 1324）和ser-7（tm 1728）无效等位基因。此外，虽然细菌泵在ser-7（tm 1325）动物中上调，泵更不规则。在分别含有5-HT样受体和色氨酸羟化酶的假定无效等位基因的ser-1（ok 345）和tph-1（mg 280）动物中也观察到维持细菌上的“快速泵送”的类似失败，这表明尽管对于细菌上的泵送的上调不是必需的，但多巴胺能信号传导“精细地”了该过程。5-HT也不能刺激ser-7（tm 1325）、ser-1（ok 345）和ser-7（hnI 325）ser-1（ok 345）动物的产卵，但只有ser-7ser-1双突变体表现出Egl表型。所有的SER-7突变体表型都通过全长ser-7：：gfp翻译融合体的表达来拯救。ser-7：：gfp在几种咽神经元中表达，包括MC、M2、M3、M4和M5以及在外阴肌肉中。有趣的是，5-HT抑制产卵和咽泵在ser-7无效突变体和5-HT抑制产卵，但不泵，取消在ser-7（tm 1325）;ser-4（ok 512）双突变体。综上所述，这些结果表明，SER-7是必不可少的5-HT刺激产卵和咽泵，但其他信号通路可能会履行类似的角色在体内。
Serotonin (5-HT) stimulates both pharyngeal pumping and egg laying in Caenorhabditis elegans. Four distinct 5-HT receptors have been partially characterized, but little is known about their function in vivo. SER-7 exhibits most sequence identity to the mammalian 5-HT7 receptors and couples to a stimulation of adenyl cyclase when expressed in COS-7 cells. However, many 5-HT7-specific agonists have low affinity for SER-7. 5-HT fails to stimulate pharyngeal pumping and the firing of the MC motorneurons in animals containing the putative ser-7(tm1324) and ser-7(tm1728) null alleles. In addition, although pumping on bacteria is upregulated in ser-7(tm1325) animals, pumping is more irregular. A similar failure to maintain "fast pumping" on bacteria also was observed in ser-1(ok345) and tph-1(mg280) animals that contain putative null alleles of a 5-HT,like receptor and tryptophan hydroxylase, respectively, suggesting that serotonergic signaling, although not essential for the upregulation Of Pumping on bacteria, "fine times" the process. 5-HT also fails to stimulate egg laying in ser-7(tm1325), ser-1(ok345), and ser-7(hnI325) ser-1(ok345) animals, but only the ser-7ser-1 double mutants exhibit an Egl phenotype. All of the SER-7 mutant phenotypes are rescued by the expression of full-length ser-7::gfp translational fusions. ser-7::gfp is expressed in several pharyngeal neurons, including the MC, M2, M3, M4, and M5, and in vulval Muscle. Interestingly, 5-HT inhibits egg laying and pharyngeal pumping in ser-7 null mutants and the 5-HT inhibition of egg laying, but not pumping, is abolished in ser-7(tm1325);ser-4(ok512) double mutants. Taken together, these results suggest that SER-7 is essential for the 5-HT stimulation of both egg laying and pharyngeal pumping, but that other signaling pathways can probably fulfill similar roles in vivo.