Genetic Control of Vacuolar H+-ATPase Expression

液泡H-ATP酶表达的遗传控制

基本信息

  • 批准号:
    6768832
  • 负责人:
  • 金额:
    $ 25.3万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    1997
  • 资助国家:
    美国
  • 起止时间:
    1997-01-01 至 2006-05-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): The vacuolar proton-translocating ATPase, or V-ATPase, is a multi-subunit complex that uses energy from ATP hydrolysis to transport protons across cellular membranes. In most eukaryotes, V-ATPases reside solely in membranes of the endocytic network, where they serve to acidify endosomes, lysosomes, the trans-Golgi, and other vacuolar compartments. However, some specialized cell types, including kidney epithelia, osteoclasts, macrophages, and neurons, express the V-ATPase at high levels and in specialized subcellular compartments, where the enzyme is critical for such diverse functions as urinary acidification, bone resorption, regulation of intracellular pH, and regulated vesicular uptake of neurotransmitters. The variety of functions performed by V-ATPases among mammalian cells is attributable to expression of multiple subunit isoforms, differences in overall expression levels, and the capacity for regulated targeting to specialized membrane compartments. Inappropriate expression of V-ATPase in humans has been shown to lead to serious disease states, including renal tubular acidosis, deafness, and osteopetrosis. The genetic controls that regulate V-ATPase expression must be varied and diverse to meet the specific proton-transport needs of many specialized cell types, as well as its constitutive role in the endocytic network. These include both transcriptional and post-transcriptonal mechansims, as well as intracellular targeting of both V-ATPase mRNA and proteins. The long-term goal of this project is to understand the mechanisms by which V-ATPases are expressed at appropriate levels and in appropriate membrane compartments. To this end, the specific aims are directed toward (1) examining mechanisms by which V-ATPase mRNA stability is regulated in proton-secreting cells such as macrophages and kidney epithelia; (2) examining determinants within V-ATPase mRNAs that mediate intracellular trafficking in specialized cell types; and (3) defining genetic elements that control expression of a uniquely regulated V-ATPase subunit involved in intracellular trafficking. These aims will be achieved through experiments in which V-ATPase mRNAs are genetically manipulated in cell culture models; the effects of these manipulations of V-ATPase expression and cell function will be determined.
描述(由申请人提供):液泡质子转运ATP酶或V-ATP酶是一种多亚基复合物,利用ATP水解产生的能量将质子转运穿过细胞膜。在大多数真核生物中,V-ATP酶仅存在于胞吞网络的膜中,在那里它们用于酸化内体、溶酶体、高尔基体和其他液泡区室。然而,一些专门的细胞类型,包括肾上皮细胞、破骨细胞、巨噬细胞和神经元,在高水平和专门的亚细胞区室中表达V-ATP酶,其中该酶对于诸如尿酸化、骨吸收、细胞内pH调节和神经递质的调节囊泡摄取等多种功能至关重要。V-ATP酶在哺乳动物细胞中发挥的多种功能可归因于多种亚基同种型的表达、总体表达水平的差异以及调节靶向特定膜区室的能力。人类中V-ATP酶的不适当表达已显示导致严重的疾病状态,包括肾小管酸中毒、耳聋和骨硬化症。 调节V-ATP酶表达的遗传控制必须是多种多样的,以满足许多专门细胞类型的特定质子运输需求,以及其在胞吞网络中的组成性作用。这些包括转录和转录后机制,以及V-ATP酶mRNA和蛋白质的细胞内靶向。该项目的长期目标是了解V-ATP酶在适当水平和适当膜隔室中表达的机制。为此,具体目标是:(1)检查质子分泌细胞(如巨噬细胞和肾上皮细胞)中V-ATP酶mRNA稳定性调节的机制;(2)检查V-ATP酶mRNA内介导特定细胞类型细胞内运输的决定簇;(3)定义控制参与细胞内运输的独特调节V-ATP酶亚基表达的遗传元件。这些目标将通过在细胞培养模型中对V-ATP酶mRNA进行遗传操作的实验来实现;将确定这些操作对V-ATP酶表达和细胞功能的影响。

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 }}

BETH S. LEE其他文献

BETH S. LEE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('BETH S. LEE', 18)}}的其他基金

Regulation of mRNA stability in Kidney epithelia
肾上皮细胞 mRNA 稳定性的调节
  • 批准号:
    7916094
  • 财政年份:
    2009
  • 资助金额:
    $ 25.3万
  • 项目类别:
DYNAMICS OF THE ACTIN CYTOSKELETON IN OSTEOCLASTS
破骨细胞中肌动蛋白细胞骨架的动力学
  • 批准号:
    7091731
  • 财政年份:
    2006
  • 资助金额:
    $ 25.3万
  • 项目类别:
DYNAMICS OF THE ACTIN CYTOSKELETON IN OSTEOCLASTS
破骨细胞中肌动蛋白细胞骨架的动力学
  • 批准号:
    7393216
  • 财政年份:
    2006
  • 资助金额:
    $ 25.3万
  • 项目类别:
DYNAMICS OF THE ACTIN CYTOSKELETON IN OSTEOCLASTS
破骨细胞中肌动蛋白细胞骨架的动力学
  • 批准号:
    7211414
  • 财政年份:
    2006
  • 资助金额:
    $ 25.3万
  • 项目类别:
DYNAMICS OF THE ACTIN CYTOSKELETON IN OSTEOCLASTS
破骨细胞中肌动蛋白细胞骨架的动力学
  • 批准号:
    7591685
  • 财政年份:
    2006
  • 资助金额:
    $ 25.3万
  • 项目类别:
TRANSCRIPTIONAL CONTROL OF VACUOLAR H+-ATPASE EXPRESSION
液泡H-ATP酶表达的转录控制
  • 批准号:
    6138044
  • 财政年份:
    1997
  • 资助金额:
    $ 25.3万
  • 项目类别:
TRANSCRIPTIONAL CONTROL OF VACUOLAR H+-ATPASE EXPRESSION
液泡H-ATP酶表达的转录控制
  • 批准号:
    2634309
  • 财政年份:
    1997
  • 资助金额:
    $ 25.3万
  • 项目类别:
TRANSCRIPTIONAL CONTROL OF VACUOLAR H+-ATPASE EXPRESSION
液泡H-ATP酶表达的转录控制
  • 批准号:
    2856807
  • 财政年份:
    1997
  • 资助金额:
    $ 25.3万
  • 项目类别:
TRANSCRIPTIONAL CONTROL OF VACUOLAR H+-ATPASE EXPRESSION
液泡H-ATP酶表达的转录控制
  • 批准号:
    2623984
  • 财政年份:
    1997
  • 资助金额:
    $ 25.3万
  • 项目类别:
TRANSCRIPTIONAL CONTROL OF VACUOLAR H+-ATPASE EXPRESSION
液泡H-ATP酶表达的转录控制
  • 批准号:
    6500071
  • 财政年份:
    1997
  • 资助金额:
    $ 25.3万
  • 项目类别:

相似海外基金

Hedgehog signalling in T-cell differentiation and function
T 细胞分化和功能中的 Hedgehog 信号传导
  • 批准号:
    BB/Y003454/1
  • 财政年份:
    2024
  • 资助金额:
    $ 25.3万
  • 项目类别:
    Research Grant
Comparative single-cell analysis of disease-derived stem cells to identify the cell fate defect on the cell differentiation trajectory
对疾病来源的干细胞进行比较单细胞分析,以确定细胞分化轨迹上的细胞命运缺陷
  • 批准号:
    23H02466
  • 财政年份:
    2023
  • 资助金额:
    $ 25.3万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
The role of cell differentiation in colorectal cancer progression
细胞分化在结直肠癌进展中的作用
  • 批准号:
    23K06661
  • 财政年份:
    2023
  • 资助金额:
    $ 25.3万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Dissecting the role of hypoxia in T cell differentiation in cancer
剖析缺氧在癌症 T 细胞分化中的作用
  • 批准号:
    10578000
  • 财政年份:
    2023
  • 资助金额:
    $ 25.3万
  • 项目类别:
Mechanisms mediating human enteroendocrine cell differentiation and function
介导人肠内分泌细胞分化和功能的机制
  • 批准号:
    10739834
  • 财政年份:
    2023
  • 资助金额:
    $ 25.3万
  • 项目类别:
TOX-driven CD8 T cell differentiation and dysfunction in tumors
TOX驱动的肿瘤中CD8 T细胞分化和功能障碍
  • 批准号:
    10586679
  • 财政年份:
    2023
  • 资助金额:
    $ 25.3万
  • 项目类别:
Elucidation of molecular mechanisms of immune cell differentiation of a novel Rab protein in hematopoietic stem cells
阐明造血干细胞中新型Rab蛋白免疫细胞分化的分子机制
  • 批准号:
    23K16122
  • 财政年份:
    2023
  • 资助金额:
    $ 25.3万
  • 项目类别:
    Grant-in-Aid for Early-Career Scientists
New strategies in cell replacement therapies for diabetes: role of USP7 in iPSC and adult organoids beta cell differentiation
糖尿病细胞替代疗法的新策略:USP7 在 iPSC 和成体类器官 β 细胞分化中的作用
  • 批准号:
    MR/X01813X/1
  • 财政年份:
    2023
  • 资助金额:
    $ 25.3万
  • 项目类别:
    Research Grant
Role of alveolar fibroblasts in extracellular matrix organization and alveolar type 1 cell differentiation
肺泡成纤维细胞在细胞外基质组织和肺泡1型细胞分化中的作用
  • 批准号:
    10731854
  • 财政年份:
    2023
  • 资助金额:
    $ 25.3万
  • 项目类别:
Exhaustive Identification of Essential Genes for Human Taste Cell Differentiation ~Development of a Method for Inducing Differentiation of Taste Buds from ES/iPS Cells~
彻底鉴定人类味觉细胞分化必需基因~开发诱导ES/iPS细胞味蕾分化的方法~
  • 批准号:
    23K09214
  • 财政年份:
    2023
  • 资助金额:
    $ 25.3万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了