Endothelial cell secretory granule exocytosis

内皮细胞分泌颗粒胞吐作用

• 批准号: MC_PC_13053
• 负责人: Tom Carter
• 金额: $ 113.75万
• 依托单位: St George's, University of London
• 依托单位国家: 英国
• 项目类别: Intramural
• 财政年份: 2013
• 资助国家: 英国
• 起止时间: 2013 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MC_PC_13053
• 关键词: Endothelial; cell; secretory; granule; exocytosis

A thin continuous layer of cells covers the inside of all our blood vessels, separating blood from our tissues and cells. Unlike other cells in the body, blood does not clot when in contact with healthy endothelial cells. This unique and vital property stems from the secretion of molecules that prevent blood coagulation, and that rapidly dissolve blood clots if they do form. The endothelium is not however a one-trick-pony; in addition to controlling blood coagulation, they play essential roles in regulating blood flow, tissue repair and growth, and inflammation within the vasculature and adjacent tissues. Endothelial cells control all of these different processes through the secretion of a large number of different molecules. In effect, the vascular endothelium functions as a highly specialised multi-tasking secretory machine that responds rapidly to changes in its local environment. Alterations to the normal secretory function of endothelial cells are though to contribute to an increased risk of hypertension and atherosclerosis; major causes of stroke and heart attacks. Our research is aimed at trying to understanding the cellular mechanisms that regulate secretion from these cells. We focus particularly on the secretion of peptides and proteins involved in the control of blood coagulation (von Willebrand factor and tissue plasminogen activator) and inflammation (p-selectin and small cytokines such as interleukin-8). We combine biochemical, molecular, cell biological and biophysical approaches to directly analyse the synthesis, storage and secretion of these molecules in single endothelial cells. Understanding how the secretory function of endothelial cells is controlled under normal conditions will shed light on the changes that occur during disease and help us to develop new strategies for the treatment of vascular disorders

一层薄薄的连续细胞层覆盖在我们所有血管的内部，将血液与我们的组织和细胞分开。与身体中的其他细胞不同，血液与健康的内皮细胞接触时不会凝结。这种独特而重要的特性源于防止血液凝结的分子的分泌，如果形成血栓，这种分子会迅速溶解。然而，内皮并不是一蹴而就的；除了控制血液凝固外，它们还在调节血液流动、组织修复和生长以及血管和邻近组织内的炎症方面发挥着至关重要的作用。内皮细胞通过分泌大量不同的分子来控制所有这些不同的过程。实际上，血管内皮细胞起着高度专业化的多任务分泌机器的作用，能够对局部环境的变化做出快速反应。然而，内皮细胞正常分泌功能的改变会增加高血压和动脉粥样硬化的风险，这是中风和心脏病发作的主要原因。我们的研究旨在试图了解调节这些细胞分泌的细胞机制。我们特别关注参与控制血液凝固(von Willebrand因子和组织纤溶酶原激活剂)和炎症(p-选择素和小细胞因子，如白细胞介素8)的多肽和蛋白质的分泌。我们结合生化、分子、细胞生物学和生物物理学的方法，直接分析这些分子在单个内皮细胞中的合成、储存和分泌。了解正常情况下内皮细胞的分泌功能是如何控制的，这将有助于我们了解疾病期间发生的变化，并帮助我们开发治疗血管疾病的新策略。

项目成果

Interaction between MyRIP and the actin cytoskeleton regulates Weibel-Palade body trafficking and exocytosis.

• DOI: 10.1242/jcs.178285
• 发表时间: 2016-02-01
• 期刊: Journal of cell science
• 影响因子: 4
• 作者: Conte IL;Hellen N;Bierings R;Mashanov GI;Manneville JB;Kiskin NI;Hannah MJ;Molloy JE;Carter T
• 通讯作者: Carter T

WPBs: making a mark and leaving a trail.

• DOI: 10.1182/blood.2019002322
• 发表时间: 2019-09-19
• 期刊: Blood
• 影响因子: 20.3
• 作者: Carter T;Bierings R
• 通讯作者: Bierings R

Fast-Response Calmodulin-Based Fluorescent Indicators Reveal Rapid Intracellular Calcium Dynamics.

• DOI: 10.1038/srep15978
• 发表时间: 2015-11-03
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Helassa N;Zhang XH;Conte I;Scaringi J;Esposito E;Bradley J;Carter T;Ogden D;Morad M;Török K
• 通讯作者: Török K

P-selectin mobility undergoes a sol-gel transition as it diffuses from exocytosis sites into the cell membrane.

• DOI: 10.1038/s41467-022-30669-x
• 发表时间: 2022-05-31
• 期刊: Nature communications
• 影响因子: 16.6

Multiple CaMKII Binding Modes to the Actin Cytoskeleton Revealed by Single-Molecule Imaging.

通过单分子成像揭示的多种CAMKII结合模式与肌动蛋白细胞骨架。

• DOI: 10.1016/j.bpj.2016.06.007
• 发表时间: 2016-07-26
• 期刊: Biophysical journal
• 影响因子: 3.4
• 作者: Khan S;Conte I;Carter T;Bayer KU;Molloy JE
• 通讯作者: Molloy JE