Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, 41345, Gothenburg, Sweden.
Department of Clinical and Movement Neurosciences, Queen Square Brain Bank for Neurological Disorders, Queen Square Institute of Neurology, University College London, London, UK.
Sci Rep. 2021 Sep 27;11(1):19115. doi: 10.1038/s41598-021-98487-7.
Amyloid precursor protein (APP) is expressed in many tissues in human, mice and in zebrafish. In zebrafish, there are two orthologues, Appa and Appb. Interestingly, some cellular processes associated with APP overlap with cilia-mediated functions. Whereas the localization of APP to primary cilia of in vitro-cultured cells has been reported, we addressed the presence of APP in motile and in non-motile sensory cilia and its potential implication for ciliogenesis using zebrafish, mouse, and human samples. We report that Appa and Appb are expressed by ciliated cells and become localized at the membrane of cilia in the olfactory epithelium, otic vesicle and in the brain ventricles of zebrafish embryos. App in ependymal cilia persisted in adult zebrafish and was also detected in mouse and human brain. Finally, we found morphologically abnormal ependymal cilia and smaller brain ventricles in appaappb mutant zebrafish. Our findings demonstrate an evolutionary conserved localisation of APP to cilia and suggest a role of App in ciliogenesis and cilia-related functions.
淀粉样前体蛋白 (APP) 在人类、小鼠和斑马鱼的许多组织中表达。在斑马鱼中，有两个直系同源物，Appa 和 Appb。有趣的是，一些与 APP 相关的细胞过程与纤毛介导的功能重叠。虽然已经报道了 APP 在体外培养细胞的初级纤毛中的定位，但我们使用斑马鱼、小鼠和人类样本研究了 APP 在运动和非运动感觉纤毛中的存在及其对纤毛发生的潜在影响。我们报告说，Appa 和 Appb 由纤毛细胞表达，并在斑马鱼胚胎的嗅上皮、耳囊和脑室中的纤毛膜上定位。顶泌细胞纤毛中的 App 在成年斑马鱼中持续存在，并在小鼠和人类大脑中也被检测到。最后，我们发现 appaappb 突变斑马鱼的室管膜纤毛形态异常和脑室内腔较小。我们的发现表明 APP 向纤毛的定位具有进化保守性，并提示 App 在纤毛发生和与纤毛相关的功能中发挥作用。
