Reiner David J, Weinshenker David, Tian Hong, Thomas James H, Nishiwaki Kiyoji, Miwa Johji, Gruninger Todd, Leboeuf Brigitte, Garcia L Rene
Department of Genome Sciences, University of Washington, Seattle, WA, USA.
J Neurogenet. 2006 Jan-Jun;20(1-2):41-66. doi: 10.1080/01677060600788826.
The Caenorhabditis elegans unc-103 gene encodes a potassium channel whose sequence is most similar to the ether-a-go-go related gene (erg) type of K+ channels. We find that the n 500 and e 1597 gain-of-function (gf) mutations in unc-103 cause reduced excitation in most muscles, while loss-of-function (lf) mutations cause mild muscle hyper-excitability. Both gf alleles change the same residue near the cytoplasmic end of S6, consistent with this region regulating channel activation. We also report additional dominant-negative and lf alleles of unc-103 that can antagonize or reduce the function of both gf and wild-type alleles. The unc-103 locus contains 6 promoter regions that express unc-103 in different combinations of body-wall and sex-specific muscles, motor-, inter- and sensory-neurons. Each promoter drives transcripts containing a unique first exon, conferring sequence variability to the N-terminus of the UNC-103 protein, while three splice variants introduce variability into the UNC-103 C-terminus. unc-103(0) hermaphrodites prematurely lay embryos that would normally be retained in the uterus and lay eggs under conditions that inhibit egg-laying behavior. In the egg-laying circuit, unc-103 is expressed in vulval muscles and the HSN neurons from different promoters. Supplying the proper UNC-103 isoform to the vulval muscles is sufficient to restore regulation to egg-laying behavior.
秀丽隐杆线虫unc-103基因编码一种钾通道,其序列与钾通道的ether-a-go-go相关基因(erg)类型最为相似。我们发现,unc-103中的n500和e1597功能获得性(gf)突变会导致大多数肌肉的兴奋性降低,而功能丧失性(lf)突变会导致肌肉轻度过度兴奋。两个gf等位基因改变了S6细胞质末端附近的相同残基,这与该区域调节通道激活一致。我们还报告了unc-103的其他显性负性和lf等位基因,它们可以拮抗或降低gf和野生型等位基因的功能。unc-103基因座包含6个启动子区域,这些区域在体壁和性别特异性肌肉、运动神经元、中间神经元和感觉神经元的不同组合中表达unc-103。每个启动子驱动包含独特第一个外显子的转录本,赋予UNC-103蛋白N端序列变异性,而三种剪接变体则使UNC-103 C端产生变异性。unc-103(0)雌雄同体线虫会过早产下通常会保留在子宫内的胚胎,并在抑制产卵行为的条件下产卵。在产卵回路中,unc-103从不同启动子在阴门肌肉和HSN神经元中表达。向阴门肌肉提供合适的UNC-103异构体足以恢复对产卵行为的调节。