PDF(Pubmed)
Abstract：
The primary cilium, an antenna-like sensory organelle that protrudes from the surface of most eukaryotic cell types, has become a signaling hub of growing interest given that defects in its structure and/or function are associated with human diseases and syndromes, known as ciliopathies. With the continuously expanding role of primary cilia in health and diseases, identifying new players in ciliogenesis will lead to a better understanding of the function of this organelle. It has been shown that the primary cilium shares similarities with the immune synapse, a highly organized structure at the interface between an antigen-presenting or target cell and a lymphocyte. Studies have demonstrated a role for known cilia regulators in immune synapse formation. However, whether immune synapse regulators modulate ciliogenesis remains elusive. Here, we find that programmed death ligand 1 (PD-L1), an immune checkpoint protein and regulator of immune synapse formation, plays a role in the regulation of ciliogenesis. We found that PD-L1 is enriched at the centrosome/basal body and Golgi apparatus of ciliated cells and depleting PD-L1 enhanced ciliogenesis and increased the accumulation of ciliary membrane trafficking proteins Rab8a, BBS5, and sensory receptor protein PC-2. Moreover, PD-L1 formed a complex with BBS5 and PC-2. In addition, we found that depletion of PD-L1 resulted in the ciliary accumulation of Gli3 and the downregulation of Gli1. Our results suggest that PD-L1 is a new player in ciliogenesis, contributing to PC-2-mediated sensory signaling and the Hh signaling cascade.
摘要：
初级纤毛,从大多数真核细胞类型的表面突出的天线状感觉细胞器，鉴于其结构和/或功能的缺陷与人类疾病和综合症有关，已成为越来越感兴趣的信号枢纽，被称为纤毛病。随着初级纤毛在健康和疾病中的作用不断扩大，识别纤毛发生中的新参与者将导致对该细胞器功能的更好理解。研究表明，初级纤毛与免疫突触有相似之处，在抗原呈递细胞或靶细胞与淋巴细胞之间的界面处的高度组织的结构。研究已经证明已知的纤毛调节因子在免疫突触形成中的作用。然而,免疫突触调节因子是否能调节纤毛生成仍然难以捉摸。这里,我们发现程序性死亡配体1(PD-L1)，一种免疫检查点蛋白和免疫突触形成的调节剂，在纤毛生成的调节中起作用。我们发现PD-L1富集在纤毛细胞的中心体/基体和高尔基体，消耗PD-L1增强了纤毛生成并增加了纤毛膜运输蛋白Rab8a的积累，BBS5和感觉受体蛋白PC-2。此外，PD-L1与BBS5和PC-2形成复合物。此外,我们发现PD-L1的耗竭导致Gli3的纤毛积累和Gli1的下调.我们的结果表明PD-L1是纤毛发生的新参与者，有助于PC-2介导的感觉信号和Hh信号级联。
