Primary cilia are located at the dendritic tips of sensory neurons and house the molecular machinery necessary for detection and transduction of sensory stimuli. The mechanisms that coordinate dendrite extension with cilium position during sensory neuron development are not well understood. Here, we show that GRDN-1, the Caenorhabditis elegans ortholog of the highly conserved scaffold and signaling protein Girdin/GIV, regulates both cilium position and dendrite extension in the postembryonic AQR and PQR gas-sensing neurons. Mutations in grdn-1 disrupt dendrite outgrowth and mislocalize cilia to the soma or proximal axonal segments in AQR, and to a lesser extent, in PQR. GRDN-1 is localized to the basal body and regulates localization of HMR-1/Cadherin to the distal AQR dendrite. However, knockdown of HMR-1 and/or loss of SAX-7/LICAM, molecules previously implicated in sensory dendrite development in C. elegans, do not alter AQR dendrite morphology or cilium position. We find that GRDN-1 localization in AQR is regulated by UNC-116/Kinesin-1, and that correspondingly, unc-116 mutants exhibit severe AQR dendrite outgrowth and cilium positioning defects. In contrast, GRDN-1 and cilium localization in PQR is modulated by LIN-44/Wnt signaling. Together, these findings identify upstream regulators of GRDN-1, and describe new cell-specific roles for this multifunctional protein in sensory neuron development.

初级纤毛位于感觉神经元的树突尖端，并容纳检测和转导感觉刺激所必需的分子机制。在感觉神经元发育过程中协调树突延伸与纤毛位置的机制尚不清楚。在这里，我们展示了 GRDN-1，即高度保守的支架和信号蛋白 Girdin/GIV 的秀丽隐杆线虫直系同源物，调节胚胎后 AQR 和 PQR 气体感应神经元中的纤毛位置和树突延伸。grdn-1中的突变在 AQR 中破坏树突生长并将纤毛错误定位到胞体或近端轴突节段，在 PQR 中的程度较小。GRDN-1 定位于基体并调节 HMR-1/钙粘蛋白在远端 AQR 树突的定位。然而，HMR-1 的敲除和/或 SAX-7/LICAM 的缺失，以前与秀丽隐杆线虫感觉树突发育有关的分子，不会改变 AQR 的树突形态或纤毛位置。我们发现 AQR 中的 GRDN-1 定位受 UNC-116/Kinesin-1 调节，相应地，unc-116突变体表现出严重的 AQR 枝晶生长和纤毛定位缺陷。相比之下，PQR 中的 GRDN-1 和纤毛定位受 LIN-44/Wnt 信号调制。总之，这些发现确定了 GRDN-1 的上游调节因子，并描述了这种多功能蛋白在感觉神经元发育中的新细胞特异性作用。