Under pressure: Ano1 mediates pressure sensing in the lymphatic system.
Under pressure: Ano1 mediates pressure sensing in the lymphatic system.
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在压力下：Ano1 介导淋巴系统中的压力感应。
DOI：
10.1085/jgp.201912320
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Carlson,AnneE
中科院分区：
文献类型：
--
作者：
Tembo,Maiwase;Carlson,AnneE
尽管11年前才被发现，但钙激活的氯−通道，ANO1，已经被确定为一种重要的生理蛋白。这个通道有很多名字--TMEM16A、DOG1、ORAOV2、TAOS2--并且参与更多的生理过程。这些由Ano1调控的过程中，有几个似乎是不同的，从粘膜分泌(Huang等人，2012年)到受精(Wozniak等人，2018年)。然而，渠道的确切作用不一定是多种多样的。事实上，Ano1在各种类型的平滑肌收缩信号中的反复作用正在出现。例如，ANO1介导副交感神经诱导的气道平滑肌的支气管收缩(Huang等人，2012年)。在子宫平滑肌中，Ano1促进自发和催产素诱导的收缩(Bernstein等人，2014)。在一些血管平滑肌中，例如大脑动脉周围的血管，ANO1介导了牵张激活的收缩(Bulley等人，2012年)。在这一期的《普通生理学杂志》上，Zawieja等人说。在淋巴系统中，淋巴管周围的平滑肌收缩能够使液体和大分子从间质间隙返回血液(Jones和Min，2011)。这些淋巴管表现出与压力相关的自发性收缩频率，因此液体积聚导致健康组织中的血管收缩。这些血管的功能障碍会导致淋巴水肿，定义为四肢液体的异常积聚(Jones和Min，2011)。由于目前还没有淋巴水肿症的治疗方法，患者不得不在余生中忍受这种疾病。更好地了解这些淋巴管收缩的分子和离子机制可能为开发治疗和逆转淋巴疾病的药物疗法铺平道路。为了探讨Ano1是否参与淋巴管收缩的调节，Zawieja等人(2019)首先证实
Although identified only 11 years ago, the Ca2+-activated Cl− channel (CaCC), Ano1, is firmly established as an essential physiological protein. This channel is known by many names—TMEM16a, DOG1, ORAOV2, TAOS2—and mediates many more physiological processes. Several of these Ano1-regulated processes are seemingly disparate, ranging from mucosal secretion (Huang et al., 2012) to fertilization (Wozniak et al., 2018). However, the precise role of the channel is not necessarily as varied. Indeed, a recurring role for Ano1 in signaling the contraction of various types of smooth muscle is emerging. For example, Ano1 mediates parasympatheticinduced bronchi contraction in airway smooth muscle (Huang et al., 2012). In uterine smooth muscle, Ano1 promotes spontaneous and oxytocin-induced contractions (Bernstein et al., 2014). In some vascular smooth muscle, such as that surrounding the cerebral artery, Ano1 mediates stretch-activated constriction (Bulley et al., 2012). In this issue of the Journal of General Physiology, Zawieja et al. describe a new role for Ano1 as a mediator of pressure-sensitive contraction in lymphatic collecting vessels.In the lymphatic system, contraction of the smooth muscle surrounding lymphatic vessels enables the return of fluid and macromolecules from the interstitial space to the blood (Jones and Min, 2011). These lymphatic vessels exhibit spontaneous contractions with a pressure-dependent frequency such that fluid build-up results in vessel contractions in healthy tissues. Dysfunction of these vessels causes lymphedemas, defined as the abnormal buildup of fluid in extremities (Jones and Min, 2011). Because there are no existing cures for lymphedemas, afflicted patients have to bear with this disorder for the rest of their lives. A better understanding of the molecular and ionic mechanisms underlying contraction of these lymphatic collecting vessels may pave the way for the development of pharmaceutical therapies to treat and reverse lymphatic disorders. To explore whether Ano1 contributes to the regulation of lymphatic vessel contraction, Zawieja et al.(2019) first confirmed