The Anaphase-Promoting Complex (APC) ubiquitin ligase affects chemosensory behavior in C. elegans.
The Anaphase-Promoting Complex (APC) ubiquitin ligase affects chemosensory behavior in C. elegans.
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作者：
Wang J;Jennings AK;Kowalski JR
神经生物学基本功能的调节与泛素信号系统(USS)有关，USS调节蛋白质的降解和活性，由E1、E2和E3酶催化。后期促进复合体(APC)是一种多亚基E3泛素连接酶，在有丝分裂后神经元中控制着不同的发育和信号过程；然而，APC在感觉功能中的潜在作用尚不清楚。在这项研究中，我们通过测试对挥发性气味物质双乙酰、吡嗪和异戊醇的趋化作用，研究了APC泛素连接酶对秀丽线虫化学感觉的影响，野生型蠕虫被吸引到这些气味中。编码APC亚单位EMB-27 APC6的两个等位基因(g48和ye143)中的任何一个发生功能突变的动物，对AWA神经元感觉到的气味物质双乙酰和吡嗪的趋化作用增强，但对AWC神经元感觉到的异戊醇的趋化作用正常。Emb-27APC6突变体的趋化性显著增加，表明APC抑制了线虫中AWA介导的化学感觉。缺乏另一个必需的APC亚基MAT-2APC1的突变体对吡嗪的趋化作用也增强；然而，MAT-2APC1突变体对双乙酰表现出野生型反应。这两个APC亚单位突变体的反应性差异可能是由于这些亚型等位基因的不同强度所致，也可能表明APC功能亚复合体的存在在这一过程中起作用。这些发现是APC介导的化学感觉调节的第一个证据，并为进一步研究APC在特定感觉神经元中的表达水平、功能和靶点奠定了基础。由于人类和线虫神经系统的相似性，APC在感觉神经元中的作用也可能促进我们对人类感觉功能和疾病的理解。
The regulation of fundamental aspects of neurobiological function has been linked to the ubiquitin signaling system (USS), which regulates the degradation and activity of proteins and is catalyzed by E1, E2, and E3 enzymes. The Anaphase-Promoting Complex (APC) is a multi-subunit E3 ubiquitin ligase that controls diverse developmental and signaling processes in post-mitotic neurons; however, potential roles for the APC in sensory function have yet to be explored. In this study, we examined the effect of the APC ubiquitin ligase on chemosensation in Caenorhabditis elegans by testing chemotaxis to the volatile odorants, diacetyl, pyrazine, and isoamyl alcohol, to which wild-type worms are attracted. Animals with loss of function mutations in either of two alleles (g48 and ye143) of the gene encoding the APC subunit EMB-27 APC6 showed increased chemotaxis towards diacetyl and pyrazine, odorants sensed by AWA neurons, but exhibited normal chemotaxis to isoamyl alcohol, which is sensed by AWC neurons. The statistically significant increase in chemotaxis in the emb-27 APC6 mutants suggests that the APC inhibits AWA-mediated chemosensation in C. elegans. Increased chemotaxis to pyrazine was also seen with mutants lacking another essential APC subunit, MAT-2 APC1; however, mat-2 APC1 mutants exhibited wild type responses to diacetyl. The difference in responsiveness of these two APC subunit mutants may be due to differential strength of these hypomorphic alleles or may indicate the presence of functional sub-complexes of the APC at work in this process. These findings are the first evidence for APC-mediated regulation of chemosensation and lay the groundwork for further studies aimed at identifying the expression levels, function, and targets of the APC in specific sensory neurons. Because of the similarity between human and C. elegans nervous systems, the role of the APC in sensory neurons may also advance our understanding of human sensory function and disease.