LOCALIZED CAMP SIGNALS IN ENDOTHELIAL CELLS

内皮细胞中的局部 CAMP 信号

• 批准号: 8169582
• 负责人: THOMAS C RICH
• 金额: $ 1.63万
• 依托单位: UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8169582
• 关键词: Buffers; Camping; Cell membrane; Cells; Computer Retrieval of Information on Scientific Projects Database; Cyclic AMP; Cyclic Nucleotides; Development; Diffusion; Endothelial Cells; Funding; Gene Expression; Goals; Grant; Institution; Laboratories; Lung; Measurement; Measures; Methods; Movement; Process; Research; Research Personnel; Resolution; Resources; Second Messenger Systems; Signal Pathway; Signal Transduction; Source; Techniques; Testing; United States National Institutes of Health; Work; base; cell type; phosphoric diester hydrolase; second messenger; Buffers; Camping; Cell membrane; Cells; Computer Retrieval of Information on Scientific Projects Database; Cyclic AMP; Cyclic Nucleotides; Development; Diffusion; Endothelial Cells; Funding; Gene Expression; Goals; Grant; Institution; Laboratories; Lung; Measurement; Measures; Methods; Movement; Process; Research; Research Personnel; Resolution; Resources; Second Messenger Systems; Signal Pathway; Signal Transduction; Source; Techniques; Testing; United States National Institutes of Health; Work; base; cell type; phosphoric diester hydrolase; second messenger

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The long-term goal of our laboratory is to understand the mechanisms by which information is encoded within second messenger signals, including Ca2+ and cAMP. These signaling pathways are known to regulate diverse processes including cellular excitability, proliferation, and gene expression. Our understanding of Ca2+ signals has increased dramatically over the last 30 years, primarily due to the development of single-cell methods for measuring intracellular Ca2+. Our understanding of cAMP signals, however, has lagged behind, largely due to the lack of high-resolution, single-cell measurement techniques. Only recently have reliable approaches for measuring cAMP signals in single cells been developed. These approaches have provided an unprecedented view of cyclic nucleotide signals near the plasma membranes of several cell types. We have used these approaches to provide evidence suggesting that the effective diffusion coefficient of cAMP is considerably slower than had been previously thought (~10,000-fold slower movement than by free diffusion alone). In addition, elegant studies demonstrated that compartmentalized cAMP signals are critical for barrier function in pulmonary microvascular endothelial cells (PMVECs). Based upon these studies, we propose testing the following working hypothesis: phosphodiesterase activity, buffering, and anomalously slow cAMP diffusion localize cAMP signals in pulmonary microvascular endothelial cells.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 我们实验室的长期目标是了解在包括CA2+和CAMP在内的第二信号信号中编码信息的机制。已知这些信号通路会调节各种过程，包括细胞兴奋性，增殖和基因表达。在过去的30年中，我们对CA2+信号的理解大大增加，这主要是由于开发了用于测量细胞内Ca2+的单细胞方法。 但是，我们对营地信号的理解落后于落后，这主要是由于缺乏高分辨率的单细胞测量技术。直到最近才开发出可靠的方法来测量单个细胞中的cAMP信号。这些方法为几种细胞类型的质膜附近的循环核苷酸信号提供了前所未有的视图。我们已经使用了这些方法来提供证据，表明cAMP的有效扩散系数比以前认为的慢得多（移动速度比单独的自由扩散慢约10,000倍）。此外，优雅的研究表明，隔间化的cAMP信号对于肺微血管内皮细胞（PMVEC）中的屏障功能至关重要。基于这些研究，我们提出了测试以下工作假设：磷酸二酯酶活性，缓冲和异常缓慢的cAMP扩散将cAMP信号定位在肺微血管内皮细胞中。