Signaling Mechanisms of TMEM16a Regulation

TMEM16a 调节的信号机制

• 批准号: 10620877
• 负责人: Anne E Carlson
• 金额: $ 7.39万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-25 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10620877
• 关键词: Binding; Blood flow; Cardiac; Cardiovascular system; Development; Disease; Electrolyte Balance; Embryo; Eukaryota; Genes; Goals; Health; Human; Knockout Mice; Lipids; Malignant Neoplasms; Mediating; Mutation; Neurons; Pathology; Phosphatidylinositol 4,5-Diphosphate; Physiological Processes; Play; Public Health; Regulation; Regulatory Pathway; Research; Role; Sensory; Signal Transduction; Therapeutic; craniofacial; design; interest; novel therapeutics; uterine contractility

The TMEM16a gene encodes for a Ca2+-activated Cl- channel that is broadly expressed in eukaryotes and plays an important role in human health and disease. TMEM16a channels are required for numerous physiologic processes, including regulation of neuronal and cardiac excitability, uterine contractility, regulation of electrolyte balance, and sensory transduction. Their importance is evidenced by the embryonic lethality of TMEM16a knockout mice, and by the association of mutations in this channel with craniofacial cancers. Aside from their Ca2+-dependent activation, it is not understood how these channels are regulated. Our lab is interested in uncovering the signaling mechanisms that modulate the activity of TMEM16a channels. Our goal is to understand the primary TMEM16a regulatory pathways, and to facilitate the development of novel therapeutic options for treating disorders caused by TMEM16a deficiencies. 1

TMEM16A基因编码钙激活的氯离子通道，该通道在真核生物和 对人类的健康和疾病起着重要的作用。TMEM16A通道适用于 生理过程，包括神经元和心脏兴奋性的调节，子宫收缩， 电解质平衡的调节和感觉转导。它们的重要性从胚胎可以看出 TMEM16A基因敲除小鼠的致死性以及该通道突变与颅面部的关联 癌症。除了它们依赖于钙离子的激活外，这些通道是如何调节的还不清楚。 我们的实验室有兴趣揭示调节TMEM16A活性的信号机制 频道。我们的目标是了解TMEM16A的主要调控途径，并促进 开发治疗由TMEM16A缺乏引起的疾病的新的治疗方案。 1

项目成果

Under pressure: Ano1 mediates pressure sensing in the lymphatic system.

在压力下：Ano1 介导淋巴系统中的压力感应。

• DOI: 10.1085/jgp.201912320
• 发表时间: 2019
• 期刊: The Journal of general physiology
• 作者: Tembo,Maiwase;Carlson,AnneE
• 通讯作者: Carlson,AnneE

The secrets of success.

成功的秘密。

• DOI: 10.7554/elife.64379
• 发表时间: 2020-12-02
• 期刊: eLife
• 影响因子: 7.7
• 作者: Komondor KM;Carlson AE
• 通讯作者: Carlson AE