The role of vang-1/Van Gogh in the ciliated neurons of C. elegans

纤毛是大多数真核细胞表面的感觉器或运动性细胞器。最近，平面细胞极性(PCP)信号被认为与纤毛的形成、取向和功能有关，PCP信号是一种成熟的沿上皮细胞表面的细胞极性调节因子。我的实验室使用线虫作为模型来研究PCP信号在神经元形态和功能中的作用。我们最近发现，核心PCP蛋白Vang-1/Van Gogh和PRKL-1/Pickle的蠕虫同源蛋白在虫头的纤毛感觉神经元(CEP神经元)或支持细胞(CEP鞘细胞)的特定亚群中表达。此外，GFP翻译融合显示Vang-1特异性积聚到位于CEP树突末端的纤毛(过渡区)。我们假设CEP神经元中的Vang-1通过一种类似PCP的机制发挥作用，该机制可能包括CEPsh细胞中的PRKL-1，以适当极化树突顶端的结构，这些结构对纤毛的形成、维持或感觉功能至关重要。因此，我们建议确定Vang-1和其他核心PCP通路成分如PRKL-1在纤毛神经元中的作用，研究需要Vang-1在纤毛过渡区的遗传和细胞通路，并识别和表征在CEP神经元纤毛中特异定位Vang-1或直接或间接与Vang-1相互作用所需的新成分。最终，这项研究计划将有助于我们更好地了解PCP样信号与纤毛之间的关系，并为PCP途径组件在神经细胞中的作用提供新的见解。

Cilia are sensory or motile organelles found on the surface of most eukaryotic cells. Recently, planar cell polarity (PCP) signaling, a well-established regulator of cellular polarity along the surface of epithelial cells, has been implicated in cilia formation, orientation, and function. My laboratory uses C. elegans as a model to investigate the role of PCP signaling in neuronal morphology and function. We have recently shown that worm orthologues of the core PCP proteins VANG-1/Van Gogh and PRKL-1/Prickle are expressed in specific subsets of ciliated sensory neurons (CEP neurons) or support cells (CEP sheath cells) in the worm head. In addition, a GFP translational fusion showed a specific accumulation of VANG-1 to the cilia (transition zone) located at the distal tip of CEP dendrites. We hypothesize that VANG-1 in CEP neurons acts through a PCP-like mechanism, that may include PRKL-1 in CEPsh cells, to properly polarize structures at the dendritic tip that are important for cilia formation, maintenance, or sensory function. We therefore propose to identify the role of VANG-1 and other core PCP pathway components like PRKL-1 in ciliated neurons, investigate genetic and cellular pathways that require VANG-1 in the transition zone of cilia, and identify and characterize new components required to specifically localize VANG-1 to cilia or interact directly or indirectly with VANG-1 in the cilia of CEP neurons. Ultimately, this research program should help us better understand the relationship between PCP-like signaling and cilia as well as provide new insight into the role of PCP pathway components in neuronal cells.