Jang Yongwoo, Oh Uhtaek
Sensory Research Center, Creative Research Initiatives, College of Pharmacy, Seoul National University, Seoul, Republic of Korea.
Sensory Research Center, Creative Research Initiatives, College of Pharmacy, Seoul National University, Seoul, Republic of Korea; Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Republic of Korea.
Cell Calcium. 2014 Jun;55(6):355-61. doi: 10.1016/j.ceca.2014.02.006. Epub 2014 Feb 15.
Fluid and electrolyte releasing from secretory epithelia are elaborately regulated by orchestrated activity of ion channels. The activity of chloride channel at the apical membrane decides on the direction and the rate of secretory fluid and electrolyte. Chloride-dependent secretion is conventionally associated with intracellular increases in two second messengers, cAMP and Ca(2+), responding to luminal purinergic and basolateral adrenergic or cholinergic stimulation. While it is broadly regarded that cAMP-dependent Cl(-) secretion is regulated by cystic fibrosis transmembrane conductance regulator (CFTR), Ca(2+)-activated Cl(-) channel (CaCC) had been veiled for quite some time. Now, Anoctamin 1 (ANO1 or TMEM16A) confers Ca(2+)-activated Cl(-) currents. Ano 1 and its paralogs have been actively investigated for multiple functions underlying Ca(2+)-activated Cl(-) efflux and fluid secretion in a variety of secretory epithelial cells. In this review, we will discuss recent advances in the secretory function and signaling of ANO1 in the secretory epithelia, such as airways, intestines, and salivary glands.
分泌上皮细胞释放的液体和电解质受到离子通道精心协调的活动的精确调节。顶端膜上氯离子通道的活动决定了分泌液和电解质的方向和速率。氯离子依赖性分泌通常与细胞内两种第二信使(环磷酸腺苷(cAMP)和钙离子(Ca(2+)))的增加有关,它们分别响应腔内嘌呤能以及基底外侧肾上腺素能或胆碱能刺激。虽然人们普遍认为cAMP依赖性氯离子分泌受囊性纤维化跨膜传导调节因子(CFTR)调控,但钙离子激活的氯离子通道(CaCC)在很长一段时间内一直未被发现。现在,anoctamin 1(ANO1或TMEM16A)可产生钙离子激活的氯离子电流。Ano 1及其旁系同源物已被积极研究,以探究其在多种分泌上皮细胞中钙离子激活的氯离子外流和液体分泌的多种功能。在本综述中,我们将讨论ANO1在气道、肠道和唾液腺等分泌上皮中的分泌功能和信号传导方面的最新进展。