Korswagen H C, van der Linden A M, Plasterk R H
Division of Molecular Biology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
EMBO J. 1998 Sep 1;17(17):5059-65. doi: 10.1093/emboj/17.17.5059.
Expression of a constitutively activated version of the heterotrimeric G protein alpha-subunit Galphas results in the swelling and vacuolization of a specific subset of ventral nerve cord motoneurons of Caenorhabditis elegans. A second site modifier (sgs-1) that completely suppresses this neuronal degeneration has been isolated. sgs-1 was cloned and was shown to encode an adenylyl cyclase which is most similar to mammalian adenylyl cyclase type IX. Mutations in sgs-1 change residues that are conserved among different adenylyl cyclases. These mutations are located in the two catalytic domains and in the first multiple transmembrane spanning region of the predicted protein. An sgs-1 reporter construct shows a general neuronal expression pattern, demonstrating that sgs-1 is expressed in the neurons that are susceptible to activated Galphas-induced cell death. A second C.elegans adenylyl cyclase gene (acy-2) was analyzed as well. In contrast to sgs-1, acy-2 shows a restricted expression pattern and loss of acy-2 function results in early larval lethality. These results suggest that SGS-1 is a target of Galphas signaling in motoneurons, whereas an interaction of Galphas with ACY-2, probably in the canal-associated neurons, is required for viability.
异源三聚体G蛋白α亚基Gαs的组成型激活形式的表达导致秀丽隐杆线虫腹侧神经索运动神经元的特定亚群肿胀和空泡化。已分离出一种完全抑制这种神经元变性的第二位点修饰基因（sgs-1）。sgs-1被克隆并显示编码一种腺苷酸环化酶，它与哺乳动物IX型腺苷酸环化酶最为相似。sgs-1中的突变改变了不同腺苷酸环化酶之间保守的残基。这些突变位于预测蛋白的两个催化结构域和第一个多个跨膜区。一个sgs-1报告构建体显示出一般的神经元表达模式，表明sgs-1在易受激活的Gαs诱导的细胞死亡影响的神经元中表达。还分析了第二个秀丽隐杆线虫腺苷酸环化酶基因（acy-2）。与sgs-1相反，acy-2显示出受限的表达模式，acy-2功能丧失导致幼虫早期致死。这些结果表明，SGS-1是运动神经元中Gαs信号传导的靶点，而Gαs与ACY-2的相互作用（可能在与运河相关的神经元中）是生存所必需的。
