Type 3 adenylyl cyclase: a key enzyme mediating the cAMP signaling in neuronal cilia.
Type 3 adenylyl cyclase: a key enzyme mediating the cAMP signaling in neuronal cilia.
复制标题
DOI：
--
复制
发表时间：
2016-09
期刊：
影响因子：
--
通讯作者：
Liyan Qiu;Robert P LeBel;D. Storm;Xuanmao Chen
中科院分区：
文献类型：
--
作者：
Liyan Qiu;Robert P LeBel;D. Storm;Xuanmao Chen
纤毛是刚性的、中心粒衍生的、基于微管的细胞器，存在于大多数脊椎动物细胞包括神经元中。它们被认为是细胞的“触角”，用于检测一系列细胞外信号，包括光子，气味，形态发生素，激素和机械力。纤毛微环境不同于大多数肌动蛋白为基础的亚细胞结构，如微绒毛或突触。在神经系统中，没有证据表明神经元纤毛处理任何突触结构。显然，神经元纤毛的结构特征不允许它们拥有任何突触连接。然而，在纤毛中发现了大量的G蛋白偶联受体（GPCR），包括气味受体、视紫红质、Smoothened和6型5-羟色胺受体，这表明这些微小的过程在很大程度上依赖于代谢型受体及其调谐信号来影响神经元功能。3型腺苷酸环化酶（AC 3），广泛称为纤毛标记物，在整个大脑的嗅觉感觉纤毛和初级纤毛中高度且主要表达。我们发现，小鼠AC 3的消融导致多效性表型，包括嗅觉丧失、无法检测气流的机械刺激、认知缺陷、肥胖和抑郁样行为。多种人类遗传证据也表明，AC 3与肥胖、重度抑郁症（MDD）、结节病和不育症有关，强调了其功能的重要性。本文就神经元纤毛中cAMP信号通路的关键酶AC 3的研究进展作一综述。
Cilia are rigid, centriole-derived, microtubule-based organelles present in a majority of vertebrate cells including neurons. They are considered the cellular "antennae" attuned for detecting a range of extracellular signals including photons, odorants, morphogens, hormones and mechanical forces. The ciliary microenvironment is distinct from most actin-based subcellular structures such as microvilli or synapses. In the nervous system, there is no evidence that neuronal cilia process any synaptic structure. Apparently, the structural features of neuronal cilia do not allow them to harbor any synaptic connections. Nevertheless, a large number of G protein-coupled receptors (GPCRs) including odorant receptors, rhodopsin, Smoothened, and type 6 serotonin receptor are found in cilia, suggesting that these tiny processes largely depend on metabotropic receptors and their tuned signals to impact neuronal functions. The type 3 adenylyl cyclase (AC3), widely known as a cilia marker, is highly and predominantly expressed in olfactory sensory cilia and primary cilia throughout the brain. We discovered that ablation of AC3 in mice leads to pleiotropic phenotypes including anosmia, failure to detect mechanical stimulation of airflow, cognitive deficit, obesity, and depression-like behaviors. Multiple lines of human genetic evidence also demonstrate that AC3 is associated with obesity, major depressive disorder (MDD), sarcoidosis, and infertility, underscoring its functional importance. Here we review recent progress on AC3, a key enzyme mediating the cAMP signaling in neuronal cilia.