The Ion Channel and GPCR Toolkit of Brain Capillary Pericytes.
The Ion Channel and GPCR Toolkit of Brain Capillary Pericytes.
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DOI：
10.3389/fncel.2020.601324
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发表时间：
2020
影响因子：
5.3
通讯作者：
Longden TA
中科院分区：
文献类型：
--
作者：
Hariharan A;Weir N;Robertson C;He L;Betsholtz C;Longden TA
脑周细胞位于毛细血管的近腔表面，其突起覆盖毛细血管床长度的约90%。这些细胞在大约150年前首次被描述（Eberth，Rouget，），近年来一直是严格的实验审查的主题，但它们的生理作用仍然不确定，并且对它们用于执行其功能的信号元件的补充知之甚少。在这篇综述中，我们综合功能数据与单细胞RNAseq屏幕探索离子通道和G蛋白偶联受体（GPCR）工具包的网格和薄股周细胞的大脑，目的是提供一个框架，更深入地探索的分子机制，支配周细胞生理。我们认为，他们的补充渠道和受体的理想位置毛细血管周细胞发挥核心作用，在适应血流，以满足从毛细血管床深处的神经元能量需求的挑战，通过使其膜电位的动态调节，影响电输出的细胞。特别是，我们概述了如何遗传和功能的证据表明，在这种情况下，GS耦合GPCR和ATP敏感钾（KATP）通道的重要作用。我们提出了一个预测模型，从周细胞到上游小动脉的远程超极化电信号，并详细说明了TRP和Ca 2+通道和Gq，Gi/o和G12/13信号传导过程，抵消了这一点。我们强调需要解决的关键问题，以进一步推进我们对毛细血管周细胞信号拓扑结构的理解，以及这如何有助于它们的生理作用和疾病中的功能障碍。
Brain pericytes reside on the abluminal surface of capillaries, and their processes cover ~90% of the length of the capillary bed. These cells were first described almost 150 years ago (Eberth,; Rouget,) and have been the subject of intense experimental scrutiny in recent years, but their physiological roles remain uncertain and little is known of the complement of signaling elements that they employ to carry out their functions. In this review, we synthesize functional data with single-cell RNAseq screens to explore the ion channel and G protein-coupled receptor (GPCR) toolkit of mesh and thin-strand pericytes of the brain, with the aim of providing a framework for deeper explorations of the molecular mechanisms that govern pericyte physiology. We argue that their complement of channels and receptors ideally positions capillary pericytes to play a central role in adapting blood flow to meet the challenge of satisfying neuronal energy requirements from deep within the capillary bed, by enabling dynamic regulation of their membrane potential to influence the electrical output of the cell. In particular, we outline how genetic and functional evidence suggest an important role for Gs-coupled GPCRs and ATP-sensitive potassium (KATP) channels in this context. We put forth a predictive model for long-range hyperpolarizing electrical signaling from pericytes to upstream arterioles, and detail the TRP and Ca2+ channels and Gq, Gi/o, and G12/13 signaling processes that counterbalance this. We underscore critical questions that need to be addressed to further advance our understanding of the signaling topology of capillary pericytes, and how this contributes to their physiological roles and their dysfunction in disease.
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影响因子：
3.5
作者：
Balsinde, J;Winstead, MV;Dennis, EA
通讯作者：
Dennis, EA
影响因子：
8.3
作者：
Aziz, Qadeer;Thomas, Alison M.;Tinker, Andrew
通讯作者：
Tinker, Andrew
影响因子：
5.5
作者：
Ballanyi, K;Doutheil, J;Brockhaus, J
通讯作者：
Brockhaus, J
DOI：
10.1111/j.1749-6632.1998.tb09636.x
发表时间：
1998-01-01
期刊：
SALIVARY GLAND BIOGENESIS AND FUNCTION
影响因子：
--
作者：
Berninsone, P;Hirschberg, CB
通讯作者：
Hirschberg, CB
影响因子：
64.8
作者：
Armulik, Annika;Genove, Guillem;Betsholtz, Christer
通讯作者：
Betsholtz, Christer