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CELL SURFACE EXPRESSION OF ACID SENSITIVE K2P CHANNELS: DISSECTING THE ENDOCYTIC AND RECYCLING PATHWAYS

酸敏感 K2P 通道的细胞表面表达：剖析内吞和再循环途径

基本信息

批准号：
BB/J008168/1
负责人：
Ita O'Kelly
金额：
$ 46.89万
依托单位：
University of Southampton
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2012
资助国家：
英国
起止时间：
2012 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=BB%2FJ008168%2F1
关键词：
CELL SURFACE EXPRESSION ACID SENSITIVE

项目摘要

All cells maintain different concentrations of ions (e.g. sodium, potassium, chloride) across their cell membrane and results in a difference in charge (called the resting membrane potential; RMP) between inside and outside the cell. This membrane potential is of critical important to every cells function. Excitable cells (e.g. heart (or cardiac), brain (or neuronal) or muscle cells) could not function without a RMP. The RMP is maintained by controlling the movement of ions between the inside and outside of the cell. Ions need to travel through specialised channels called ion channels to move from one side of the cell membrane to the other. This proposal focuses on an ion channel that is key to maintaining the RMP of cells, these channels are called two-pore domain potassium (K2P) channels. K2P channels allow potassium ions to pass from the inside of the cell to the outside thus helping the cell maintain its appropriate RMP. These channels have been implicated in playing roles in the response of cardiac and neuronal cells to substances such as drugs and anaesthetics as well as natural substances like hormones, neurotransmitters and changes in oxygen tension. An important feature of K2P channels is that once at the surface of the cell these channels are active and allow potassium to move from areas of high potassium concentration (inside the cell) to areas of low potassium concentration (outside the cell). Because these channels allow potassium to leak out of the cell once they are inserted into the cell membrane it is critical to closely regulate the number of K2P channels on the cell surface at any given time. Similarly it is important to understand how the cell increases or decreases the number of the channels at the cell surface in response to different environmental messages or needs. The work in my laboratory focuses on the different ways a cell can control the production and delivery of ion channels to the correct location within the cell. The focus of this proposal is on the mechanisms the cell uses to retrieve K2P channels from the cell surface and how this process can be disrupted or regulated. This is important as understanding the balance between channel delivery to and recovery from the cell surface will provide critical understanding of the mechanism by which cells control not only their RMP but their ability to respond to their environment and perform their cellular functions.

所有细胞在其细胞膜上维持不同浓度的离子（例如钠、钾、氯），并导致细胞内外的电荷差异（称为静息膜电位; RMP）。这种膜电位对每个细胞的功能至关重要。可兴奋细胞（例如心脏（或心脏）、脑（或神经元）或肌肉细胞）在没有RMP的情况下无法发挥功能。通过控制细胞内外离子的运动来维持RMP。离子需要通过称为离子通道的专门通道从细胞膜的一侧移动到另一侧。该提议集中于维持细胞RMP的关键离子通道，这些通道被称为双孔结构域钾（K2 P）通道。K2 P通道允许钾离子从细胞内部传递到外部，从而帮助细胞维持其适当的RMP。这些通道在心脏和神经细胞对药物和麻醉剂等物质以及激素、神经递质和氧张力变化等天然物质的反应中发挥作用。K2 P通道的一个重要特征是，一旦在细胞表面，这些通道是活跃的，并允许钾从高钾浓度的区域（细胞内）移动到低钾浓度的区域（细胞外）。由于这些通道一旦插入细胞膜就允许钾从细胞中泄漏出来，因此在任何给定时间密切调节细胞表面上的K2 P通道的数量是至关重要的。同样，了解细胞如何增加或减少细胞表面的通道数量以响应不同的环境信息或需求也很重要。我实验室的工作重点是细胞控制离子通道产生和输送到细胞内正确位置的不同方式。该提案的重点是细胞用于从细胞表面检索K2 P通道的机制，以及如何破坏或调节这一过程。这是重要的，因为理解通道递送到细胞表面和从细胞表面恢复之间的平衡将提供对细胞不仅控制其RMP而且控制其响应其环境和执行其细胞功能的能力的机制的关键理解。

项目成果

期刊论文数量（6）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Glutamate cycling may drive organic anion transport on the basal membrane of human placental syncytiotrophoblast.

谷氨酸循环可能驱动有机阴离子在人胎盘合成细胞基底膜上的转运。

DOI：
10.1113/jp270743
发表时间：
2015-10-15
期刊：
The Journal of physiology
影响因子：
0
作者：
Lofthouse EM;Brooks S;Cleal JK;Hanson MA;Poore KR;O'Kelly IM;Lewis RM
通讯作者：
Lewis RM

Acid sensitive background potassium channels K2P3.1 and K2P9.1 undergo rapid dynamin-dependent endocytosis.

酸敏感背景钾通道 K2P3.1 和 K2P9.1 经历快速动力依赖性内吞作用。

DOI：
10.4161/chan.25120
发表时间：
2013
期刊：
Channels (Austin, Tex.)
影响因子：
0
作者：
Mant A
通讯作者：
Mant A

AMMECR1: a single point mutation causes developmental delay, midface hypoplasia and elliptocytosis.

DOI：
10.1136/jmedgenet-2016-104100
发表时间：
2017-04
期刊：
Journal of medical genetics
影响因子：
4
作者：
Andreoletti G;Seaby EG;Dewing JM;O'Kelly I;Lachlan K;Gilbert RD;Ennis S
通讯作者：
Ennis S

The Cyclooctadepsipeptide Anthelmintic Emodepside Differentially Modulates Nematode, Insect and Human Calcium-Activated Potassium (SLO) Channel Alpha Subunits.

DOI：
10.1371/journal.pntd.0004062
发表时间：
2015
期刊：
PLoS neglected tropical diseases
影响因子：
3.8
作者：
Crisford A;Ebbinghaus-Kintscher U;Schoenhense E;Harder A;Raming K;O'Kelly I;Ndukwe K;O'Connor V;Walker RJ;Holden-Dye L
通讯作者：
Holden-Dye L