Novel Roles for Phosphoinositide Signaling in alpha-Granule Biogenesis

磷酸肌醇信号传导在 α 颗粒生物发生中的新作用

基本信息

  • 批准号:
    10656287
  • 负责人:
  • 金额:
    $ 50.45万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2020
  • 资助国家:
    美国
  • 起止时间:
    2020-05-10 至 2025-04-30
  • 项目状态:
    未结题

项目摘要

Phosphorylated phosphatidylinositols (phosphoinositides) are a type of membrane bound phospholipid that impact multiple diverse processes required for megakaryopoiesis and the activation of platelets. We have recently published in Developmental Cell that phosphoinositides in neuronal cells initiate intracellular trafficking by recruiting effector proteins such as GOLPH3 that are involved in vesicular fusion and budding of plasma membranes during Golgi biogenesis. Since megakaryocyte α-granules are derived from the trans-Golgi network and Multi-Vesicular Bodies, I hypothesize that phosphoinositide signaling is necessary for the intracellular trafficking required for the biogenesis of α-granules. PhosphatidylInositol Transfer Proteins (PITPs) are members of a small protein family that bind and transfer phosphoinositide monomers from one cellular compartment to another and thereby enable phosphoinositide synthesis. We have made the unexpected observation that the two predominant PITP isoforms found within megakaryocytes, PITPα and PITPβ play previously unrecognized but essential roles in the trafficking of cargo from the Multi-Vesicular Body to α-granules. Loss of PITP-mediated phosphoinositide synthesis produces morphologic defects similar to what is seen in humans with Gray Platelet Syndrome. The overall hypothesis of this Proposal is that phosphoinositide signaling mediated by PITPs is necessary for the membrane dynamics and protein trafficking required for the biogenesis and maintenance of megakaryocyte α-granules. In Aim 1 of the Project, we will rigorously analyze the discrete biochemical properties of individual PITP isoforms in megakaryocytes. Our preliminary data shows that the two PITP isoforms control phosphoinositide signaling through biochemically distinct mechanisms. In Aim 2, we will determine how phosphoinositide signaling contributes to alpha granule biogenesis and function. In conjunction with Project 2, we will test the hypothesis that phosphoinositide synthesis within discrete microdomains of megakaryocytes and platelets regulates effector proteins such as NBEAL2 (the mutated protein responsible for the Gray Platelet Syndrome). This signaling cascade modulates NBEAL2’s ability to mediate membrane dynamics and protein trafficking. We will also analyze in detail the functional roles of α- granules with ex vivo rheologic and ultramicroscopy studies that will be performed with Project 2, in vivo thrombosis studies with Project 3, and in vivo inflammation studies with Project 4.
磷酸化磷脂酰肌醇(磷酸肌醇)是一种膜结合的类型

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 }}

CHARLES S. ABRAMS其他文献

CHARLES S. ABRAMS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('CHARLES S. ABRAMS', 18)}}的其他基金

The Novel Mechanisms of Thrombosis Formation in Myeloproliferative Diseases
骨髓增生性疾病血栓形成的新机制
  • 批准号:
    10424485
  • 财政年份:
    2020
  • 资助金额:
    $ 50.45万
  • 项目类别:
The Novel Mechanisms of Thrombosis Formation in Myeloproliferative Diseases
骨髓增生性疾病血栓形成的新机制
  • 批准号:
    10187644
  • 财政年份:
    2020
  • 资助金额:
    $ 50.45万
  • 项目类别:
Novel Roles for Phosphoinositide Signaling in alpha-Granule Biogenesis
磷酸肌醇信号传导在 α 颗粒生物发生中的新作用
  • 批准号:
    9884351
  • 财政年份:
    2020
  • 资助金额:
    $ 50.45万
  • 项目类别:
The Novel Mechanisms of Thrombosis Formation in Myeloproliferative Diseases
骨髓增生性疾病血栓形成的新机制
  • 批准号:
    10627990
  • 财政年份:
    2020
  • 资助金额:
    $ 50.45万
  • 项目类别:
Novel Roles for Phosphoinositide Signaling in alpha-Granule Biogenesis
磷酸肌醇信号传导在 α 颗粒生物发生中的新作用
  • 批准号:
    10161821
  • 财政年份:
    2020
  • 资助金额:
    $ 50.45万
  • 项目类别:
Novel Roles for Phosphoinositide Signaling in alpha-Granule Biogenesis
磷酸肌醇信号传导在 α 颗粒生物发生中的新作用
  • 批准号:
    10434809
  • 财政年份:
    2020
  • 资助金额:
    $ 50.45万
  • 项目类别:
Platelet signals and their interface with the external environment
血小板信号及其与外部环境的接口
  • 批准号:
    8909166
  • 财政年份:
    2014
  • 资助金额:
    $ 50.45万
  • 项目类别:
Platelet signals and their interface with the external environment
血小板信号及其与外部环境的接口
  • 批准号:
    8742306
  • 财政年份:
    2014
  • 资助金额:
    $ 50.45万
  • 项目类别:
Platelet signals and their interface with the external environment
血小板信号及其与外部环境的接口
  • 批准号:
    9315871
  • 财政年份:
    2014
  • 资助金额:
    $ 50.45万
  • 项目类别:
The Biological Roles of Phoshadylinositol Transfer Proteins in Platelets
血小板中磷脂肌醇转移蛋白的生物学作用
  • 批准号:
    8257824
  • 财政年份:
    2012
  • 资助金额:
    $ 50.45万
  • 项目类别:

相似海外基金

How Does Particle Material Properties Insoluble and Partially Soluble Affect Sensory Perception Of Fat based Products
不溶性和部分可溶的颗粒材料特性如何影响脂肪基产品的感官知觉
  • 批准号:
    BB/Z514391/1
  • 财政年份:
    2024
  • 资助金额:
    $ 50.45万
  • 项目类别:
    Training Grant
BRC-BIO: Establishing Astrangia poculata as a study system to understand how multi-partner symbiotic interactions affect pathogen response in cnidarians
BRC-BIO:建立 Astrangia poculata 作为研究系统,以了解多伙伴共生相互作用如何影响刺胞动物的病原体反应
  • 批准号:
    2312555
  • 财政年份:
    2024
  • 资助金额:
    $ 50.45万
  • 项目类别:
    Standard Grant
RII Track-4:NSF: From the Ground Up to the Air Above Coastal Dunes: How Groundwater and Evaporation Affect the Mechanism of Wind Erosion
RII Track-4:NSF:从地面到沿海沙丘上方的空气:地下水和蒸发如何影响风蚀机制
  • 批准号:
    2327346
  • 财政年份:
    2024
  • 资助金额:
    $ 50.45万
  • 项目类别:
    Standard Grant
Graduating in Austerity: Do Welfare Cuts Affect the Career Path of University Students?
紧缩毕业:福利削减会影响大学生的职业道路吗?
  • 批准号:
    ES/Z502595/1
  • 财政年份:
    2024
  • 资助金额:
    $ 50.45万
  • 项目类别:
    Fellowship
感性個人差指標 Affect-X の構築とビスポークAIサービスの基盤確立
建立个人敏感度指数 Affect-X 并为定制人工智能服务奠定基础
  • 批准号:
    23K24936
  • 财政年份:
    2024
  • 资助金额:
    $ 50.45万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Insecure lives and the policy disconnect: How multiple insecurities affect Levelling Up and what joined-up policy can do to help
不安全的生活和政策脱节:多种不安全因素如何影响升级以及联合政策可以提供哪些帮助
  • 批准号:
    ES/Z000149/1
  • 财政年份:
    2024
  • 资助金额:
    $ 50.45万
  • 项目类别:
    Research Grant
How does metal binding affect the function of proteins targeted by a devastating pathogen of cereal crops?
金属结合如何影响谷类作物毁灭性病原体靶向的蛋白质的功能?
  • 批准号:
    2901648
  • 财政年份:
    2024
  • 资助金额:
    $ 50.45万
  • 项目类别:
    Studentship
Investigating how double-negative T cells affect anti-leukemic and GvHD-inducing activities of conventional T cells
研究双阴性 T 细胞如何影响传统 T 细胞的抗白血病和 GvHD 诱导活性
  • 批准号:
    488039
  • 财政年份:
    2023
  • 资助金额:
    $ 50.45万
  • 项目类别:
    Operating Grants
New Tendencies of French Film Theory: Representation, Body, Affect
法国电影理论新动向:再现、身体、情感
  • 批准号:
    23K00129
  • 财政年份:
    2023
  • 资助金额:
    $ 50.45万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
The Protruding Void: Mystical Affect in Samuel Beckett's Prose
突出的虚空:塞缪尔·贝克特散文中的神秘影响
  • 批准号:
    2883985
  • 财政年份:
    2023
  • 资助金额:
    $ 50.45万
  • 项目类别:
    Studentship
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了