Fujiwara Manabi, Hino Takahiro, Miyamoto Ryuta, Inada Hitoshi, Mori Ikue, Koga Makoto, Miyahara Koji, Ohshima Yasumi, Ishihara Takeshi
Department of Biology, Graduate School of Science, Kyushu University,
Department of Biology, Graduate School of Science, Kyushu University.
Genetics. 2015 Dec;201(4):1497-510. doi: 10.1534/genetics.115.177543. Epub 2015 Oct 4.
The body size of Caenorhabditis elegans is thought to be controlled by sensory inputs because many mutants with sensory cilium structure defects exhibit small body size. The EGL-4 cGMP-dependent protein kinase acts in sensory neurons to reduce body size when animals fail to perceive sensory signals. In addition to body size control, EGL-4 regulates various other behavioral and developmental pathways, including those involved in the regulation of egg laying and chemotaxis behavior. Here we have identified gcy-12, which encodes a receptor-type guanylyl cyclase, as a gene involved in the sensory regulation of body size. Analyses with GFP fusion constructs showed that gcy-12 is expressed in several sensory neurons and localizes to sensory cilia. Genetic analyses indicated that GCY-12 acts upstream of EGL-4 in body size control but does not affect other EGL-4 functions. Our studies indicate that the function of the GCY-12 guanylyl cyclase is to provide cGMP to the EGL-4 cGMP-dependent kinase only for limited tasks including body size regulation. We also found that the PDE-2 cyclic nucleotide phosphodiesterase negatively regulates EGL-4 in controlling body size. Thus, the cGMP level is precisely controlled by GCY-12 and PDE-2 to determine body size through EGL-4, and the defects in the sensory cilium structure may disturb the balanced control of the cGMP level. The large number of guanylyl cyclases encoded in the C. elegans genome suggests that EGL-4 exerts pleiotropic effects by partnering with different guanylyl cyclases for different downstream functions.
秀丽隐杆线虫的体型被认为受感觉输入控制，因为许多具有感觉纤毛结构缺陷的突变体表现出体型较小。当动物无法感知感觉信号时，EGL-4环磷酸鸟苷（cGMP）依赖性蛋白激酶在感觉神经元中发挥作用以减小体型。除了体型控制外，EGL-4还调节各种其他行为和发育途径，包括那些参与产卵和趋化行为调节的途径。在这里，我们鉴定出gcy-12，它编码一种受体型鸟苷酸环化酶，是参与体型感觉调节的基因。用绿色荧光蛋白（GFP）融合构建体进行的分析表明，gcy-12在几个感觉神经元中表达并定位于感觉纤毛。遗传分析表明，GCY-12在体型控制中作用于EGL-4的上游，但不影响EGL-4的其他功能。我们的研究表明，GCY-12鸟苷酸环化酶的功能是仅为包括体型调节在内的有限任务向EGL-4 cGMP依赖性激酶提供cGMP。我们还发现，PDE-2环核苷酸磷酸二酯酶在控制体型方面对EGL-4起负调节作用。因此，cGMP水平由GCY-12和PDE-2精确控制，以通过EGL-4确定体型，并且感觉纤毛结构的缺陷可能会扰乱cGMP水平的平衡控制。秀丽隐杆线虫基因组中编码的大量鸟苷酸环化酶表明，EGL-4通过与不同的鸟苷酸环化酶合作以实现不同的下游功能而发挥多效性作用。
