CELLULAR ROLE OF GRANINS IN HORMONE AND NEUROTRANSMITTER STORAGE AND R
谷粒蛋白在激素和神经递质储存和 R 中的细胞作用
基本信息
- 批准号:7601093
- 负责人:
- 金额:$ 0.54万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2007
- 资助国家:美国
- 起止时间:2007-05-01 至 2008-04-30
- 项目状态:已结题
- 来源:
- 关键词:Adrenal MedullaBiogenesisC-terminalCellsChimera organismChromaffin CellsChromaffin granuleChromogranin AChromograninsComputer Retrieval of Information on Scientific Projects DatabaseEndocrineExocytosisFamilyFundingGrantHormonesInstitutionLuminescent ProteinsMediatingMembraneMolecularMusNeuroendocrine CellNeuronsNeurosecretory SystemsNeurotransmittersNumbersOrganellesPHluorinPathway interactionsPeptide FragmentsProtein RegionProteinsProteolytic ProcessingRecruitment ActivityReportingResearchResearch PersonnelResourcesRoleSecretory VesiclesSeriesSorting - Cell MovementSourceStructureSympathetic Nervous SystemTestingTotal Internal Reflection FluorescentUnited States National Institutes of HealthVariantchromogranin Bchromogranin Cnovelresponsesecretograninssecretory proteintraffickingvacuolar H+-ATPase
项目摘要
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 chromogranins/secretogranins (granins) are a family of regulated secretory proteins widely distributed in dense-core secretory granules (DCGs) of neuroendocrine, endocrine, and neuronal cells, and includes chromogranin A (CgA), chromogranin B (CgB), and secretogranin II (SgII). Granins function as pro-hormones, giving rise by proteolytic processing to biologically active peptide fragments. Recent evidence suggests that granins may be required for the biogenesis of DCGs, and hormone sequestration in neuroendocrine cells. Using a series of novel granin chimeric photoproteins, we aim to provide a molecular definition of the cellular role of granins in hormone and neurotransmitter storage and release within the sympathetic nervous system, and the adrenal medulla.
This project aims to characterize the contribution of CgA to the initiation and formation of DCGs in sympathoadrenal chromaffin cells, and to identify putative granulogenic determinant(s) within the primary structure of this granin.
We previously reported that information necessary for CgA trafficking within the regulated pathway of chromaffin cells is contained in the amino-terminal region (CgA1-115) of the granin1. More recently, we have shown that a V-ATPase-mediated acidification of the TGN and/or the immature chromaffin granule contributes to the sorting of CgA to the regulated secretory pathway2 and to the biogenesis of DCGs by a mechanism that may recruit a sorting/granulogenic determinant located within CgA1-115, but not the C-terminal region of the protein 2, 3
We will test the hypothesis that CgA may rescue the formation of secretory granules in secretory organelle-deficient chromaffin cells, and a particular motif (cis determinant) within the primary structure of CgA is essential for such granulogenic role. We propose to express a series of CgA domains fused to EGFP or pHluorin in secretory organelle-deficient chromaffin cells, to investigate and characterize granulogenic cis determinant(s) within the primary structure of CgA. Responses to be investigated include secretagogue-stimulated exocytosis of transiently transfected CgA chimera by TIRF microscopy.
The studies will be initially conducted in the sympathoadrenal cell variant A35C, which lacks DCGs and a regulated secretory pathway, and does not express several membrane or soluble secretory granule proteins, including CgA, CgB, and SgII 4. We will extend these studies to primary culture of chromaffin cells isolated from CgA-/- KO mice, which show reduced DCGs number.
这个子项目是许多研究子项目中利用
资源由NIH/NCRR资助的中心拨款提供。子项目和
调查员(PI)可能从NIH的另一个来源获得了主要资金,
并因此可以在其他清晰的条目中表示。列出的机构是
该中心不一定是调查人员的机构。
嗜铬颗粒蛋白/分泌颗粒蛋白是一类广泛分布于神经内分泌、内分泌和神经细胞的致密核分泌颗粒(DCGS)的分泌蛋白家族,包括嗜铬颗粒蛋白A(CgA)、嗜铬颗粒蛋白B(CgB)和分泌颗粒蛋白II(SgII)。Granins作为激素前体,通过蛋白质分解过程产生具有生物活性的多肽片段。最近的证据表明,颗粒素可能是DCGS的生物发生和神经内分泌细胞中的激素隔离所必需的。使用一系列新的颗粒素嵌合光蛋白,我们的目标是提供颗粒素在交感神经系统和肾上腺髓质内激素和神经递质储存和释放中的细胞作用的分子定义。
本项目旨在研究CgA在交感肾上腺嗜铬细胞DCGS的形成和启动中的作用,并在该颗粒的一级结构中确定可能的粒系决定因素(S)。
我们以前报道过,在嗜铬细胞的调控途径中,CGA运输所需的信息包含在颗粒蛋白1的氨基末端区域(CgA1-115)。最近,我们已经证明,V-ATPase介导的TGN和/或未成熟嗜铬粒的酸化有助于CGA对调节的分泌途径2的分选和DCGS的生物发生,其机制可能是招募位于CgA1-115内的分选/粒形成决定因素,而不是蛋白质2,3的C-末端区域
我们将检验这一假设,即CGA可能挽救分泌细胞器缺陷的嗜铬细胞中分泌颗粒的形成,并且CGA初级结构中的一个特定基序(顺式决定簇)对于这种颗粒发生作用是必不可少的。我们建议在分泌细胞器缺陷的嗜铬细胞中表达一系列与EGFP或PHluorin融合的CGA结构域,以研究和表征CGA一级结构中的粒细胞顺式决定簇(S)。在TIRF显微镜下研究的反应包括促分泌剂刺激瞬时转染的CGA嵌合体的胞吐作用。
这些研究将首先在交感肾上腺细胞变异体A35C中进行,它缺乏DCGS和调节的分泌途径,并且不表达几种膜或可溶性分泌颗粒蛋白,包括CGA、CGB和SgII 4。我们将把这些研究扩展到从CGA-/-KO小鼠分离的嗜铬细胞的原代培养,这些细胞显示DCGS数量减少。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
LAURENT TAUPENOT其他文献
LAURENT TAUPENOT的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('LAURENT TAUPENOT', 18)}}的其他基金
Trafficking of catecholamine storage vesicle proteins
儿茶酚胺储存囊泡蛋白的贩运
- 批准号:
7844957 - 财政年份:2009
- 资助金额:
$ 0.54万 - 项目类别:
CELLULAR ROLE OF GRANINS IN HORMONE AND NEUROTRANSMITTER STORAGE AND R
谷粒蛋白在激素和神经递质储存和 R 中的细胞作用
- 批准号:
7957615 - 财政年份:2009
- 资助金额:
$ 0.54万 - 项目类别:
CELLULAR ROLE OF GRANINS IN HORMONE AND NEUROTRANSMITTER STORAGE AND R
谷粒蛋白在激素和神经递质储存和 R 中的细胞作用
- 批准号:
7722437 - 财政年份:2008
- 资助金额:
$ 0.54万 - 项目类别:
Trafficking of catecholamine storage vesicle proteins
儿茶酚胺储存囊泡蛋白的贩运
- 批准号:
7122644 - 财政年份:2005
- 资助金额:
$ 0.54万 - 项目类别:
Traffic of catecholamine storage vesicle proteins
儿茶酚胺储存囊泡蛋白的运输
- 批准号:
6772916 - 财政年份:2004
- 资助金额:
$ 0.54万 - 项目类别:
Traffic of catecholamine storage vesicle proteins
儿茶酚胺储存囊泡蛋白的运输
- 批准号:
6858705 - 财政年份:2004
- 资助金额:
$ 0.54万 - 项目类别:
STIMULUS-EVENT COUPLING IN CHROMAFFIN SECRETORY GRANULES
嗜铬分泌颗粒中的刺激事件耦合
- 批准号:
6517915 - 财政年份:2001
- 资助金额:
$ 0.54万 - 项目类别:
STIMULUS-EVENT COUPLING IN CHROMAFFIN SECRETORY GRANULES
嗜铬分泌颗粒中的刺激事件耦合
- 批准号:
6635378 - 财政年份:2001
- 资助金额:
$ 0.54万 - 项目类别:
STIMULUS-EVENT COUPLING IN CHROMAFFIN SECRETORY GRANULES
嗜铬分泌颗粒中的刺激事件耦合
- 批准号:
6322497 - 财政年份:2001
- 资助金额:
$ 0.54万 - 项目类别:
Trafficking of catecholamine storage vesicle proteins
儿茶酚胺储存囊泡蛋白的贩运
- 批准号:
7430286 - 财政年份:
- 资助金额:
$ 0.54万 - 项目类别:
相似国自然基金
UMSC-Exo通过调控Ribosome biogenesis诱导心肌再生的策略及机制研究
- 批准号:82370264
- 批准年份:2023
- 资助金额:49 万元
- 项目类别:面上项目
活体动物线粒体biogenesis、fission及fusion对肝脏再生中能量供应影响机制的研究
- 批准号:81470878
- 批准年份:2014
- 资助金额:73.0 万元
- 项目类别:面上项目
相似海外基金
Biogenesis of the mitochondrial beta-barrel membrane protein at the intermembrane space.
膜间空间线粒体β-桶膜蛋白的生物发生。
- 批准号:
24K18071 - 财政年份:2024
- 资助金额:
$ 0.54万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
白血病幹細胞におけるRibosomal biogenesisの解明と治療戦略の構築
白血病干细胞核糖体生物发生的阐明和治疗策略的开发
- 批准号:
24H00639 - 财政年份:2024
- 资助金额:
$ 0.54万 - 项目类别:
Grant-in-Aid for Scientific Research (A)
New mechanisms regulating the biogenesis of extracellular vesicles
调节细胞外囊泡生物发生的新机制
- 批准号:
DP240101427 - 财政年份:2024
- 资助金额:
$ 0.54万 - 项目类别:
Discovery Projects
DEL-1 Promotes Biogenesis of Mineralizing Extracellular Vesicles by Mediating Intracellular Calcium Signaling
DEL-1 通过介导细胞内钙信号传导促进矿化细胞外囊泡的生物合成
- 批准号:
24K19876 - 财政年份:2024
- 资助金额:
$ 0.54万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
MFB: Characterization of the Biogenesis, Uptake, and Cellular Response to the Ribonucleoprotein Cargoes of Extracellular Vesicles using EV-CLASP
MFB:使用 EV-CLASP 表征细胞外囊泡核糖核蛋白货物的生物合成、摄取和细胞反应
- 批准号:
2330665 - 财政年份:2024
- 资助金额:
$ 0.54万 - 项目类别:
Standard Grant
Mechanisms of PIKII-dependent transport during secretory granule biogenesis
分泌颗粒生物发生过程中 PIKII 依赖性运输的机制
- 批准号:
490594 - 财政年份:2023
- 资助金额:
$ 0.54万 - 项目类别:
Operating Grants
MITOCHONDRIA REDOX BIOGENESIS AND METABOLIC RAMAN IMAGING IN INSULIN SIGNALLING
胰岛素信号传导中的线粒体氧化还原生物发生和代谢拉曼成像
- 批准号:
2883511 - 财政年份:2023
- 资助金额:
$ 0.54万 - 项目类别:
Studentship
Changes in structure and biogenesis of Gram-negative envelope following a polymyxin challenge
多粘菌素攻击后革兰氏阴性包膜的结构和生物发生的变化
- 批准号:
BB/X000370/1 - 财政年份:2023
- 资助金额:
$ 0.54万 - 项目类别:
Research Grant
Molecular Mechanisms of Mitochondrial Biogenesis
线粒体生物发生的分子机制
- 批准号:
10735778 - 财政年份:2023
- 资助金额:
$ 0.54万 - 项目类别: