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

vang-1/Van Gogh 在秀丽隐杆线虫纤毛神经元中的作用

• 批准号: 312460-2012
• 负责人: Colavita, Antonio
• 金额: $ 1.89万
• 依托单位: University of Ottawa
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2013
• 资助国家: 加拿大
• 起止时间: 2013-01-01 至 2014-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=526525
• 关键词: role; vang; Van; Gogh; ciliated

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.

纤毛是在大多数真核细胞表面发现的感觉或动细胞器。最近，平面细胞极性（PCP）信号传导是沿上皮细胞表面的细胞极性调节剂，与纤毛形成，方向和功能有关。我的实验室使用秀丽隐杆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。我们最近表明，核心PCP蛋白的蠕虫直系同源物VANG-1/van Gogh和Prkl-1/刺激物在蠕虫头的纤毛感觉神经元（CEP神经元）或支持细胞（CEP鞘细胞）的特定子集中表达。此外，GFP翻译融合显示了Vang-1的特异性积累到位于CEP树突远端的纤毛（过渡区）。我们假设CEP神经元中的VANG-1通过类似PCP的机制起作用，该机制可能包括CEPSH细胞中的PRKL-1，以适当地在树突状尖端上对结构进行偏振，这对于纤毛形成，维持或感觉功能很重要。因此，我们建议确定VANG-1和其他核心PCP途径组件（如PRKL-1）在纤毛神经元中的作用，研究需要在纤毛过渡区域中需要Vang-1的遗传和细胞途径，并识别和表征并表征并表征和表征与cilia或与Vang-1直接或与Vang-1直接相互作用的Vang-1所需的新组件。最终，该研究计划应帮助我们更好地了解PCP样信号传导与纤毛之间的关系，并提供对PCP途径成分在神经元细胞中的作用的新见解。