Administrative Equipment Supplement for GM135160

GM135160 行政设备补充

基本信息

  • 批准号:
    10387434
  • 负责人:
  • 金额:
    $ 9万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2019
  • 资助国家:
    美国
  • 起止时间:
    2019-12-01 至 2024-11-30
  • 项目状态:
    已结题

项目摘要

PROJECT SUMMARY Cellular shape change is a fundamental characteristic of metazoan cells that is key to development, physiology, and pathology. The formation and plasticity of neural networks are key examples of cell shape change during development and physiology, whereas cell shape and motility goes awry in cancers such as melanoma. The active control of the cytoskeleton is acknowledged as critical to cellular shape change, whereas the concurrent remodeling of the plasma membrane is perhaps less well appreciated. Although many cytoskeletal and membrane remodeling components are known and their biochemical and structural characteristics described, we lack a systematic understanding of how these disparate systems are regulated and coordinated to orchestrate cellular shape change. Perhaps the most important problem in cell morphogenesis is understanding how cells perceive cues in their environment and convert this extracellular information into shape changes through coordinated cytoskeletal dynamics and plasma membrane remodeling. Functions of small GTPases and kinases are well studied in regulating cytoskeletal dynamics and membrane remodeling. Work from my lab identified an emerging role for E3 ubiquitin ligases in regulated cellular shape change. We identified two E3 ubiquitin ligases, TRIM9 and TRIM67, which regulate cytoskeletal and exocytic proteins and cellular shape changes in response to netrin. Netrin is an extracellular morphogen that promotes neuronal morphogenesis and the progression of cancers, such as melanoma. TRIM9 and TRIM67 thus provided an excellent entry point for the lab to investigate how cytoskeletal and membrane remodeling are coordinated during netrin triggered morphogenesis and motility. TRIM9 and TRIM67 share similar sequences, localization, and interaction partners, however our studies identified distinct functions of these related proteins and antagonistic phenotypes associated with their deletion. The overarching goal of this program is to test the hypothesis that TRIM9 and TRIM67 coordinate cytoskeletal dynamics and exocytosis during netrin-dependent morphogenesis in neurons and migrating melanoma cells. Our work will provide fundamental mechanistic understanding of the regulation of the cytoskeleton and membrane trafficking during development and metastasis.
项目摘要 细胞形状变化是后生动物细胞的一个基本特征,这是发育的关键, 生理学和病理学。神经网络的形成和可塑性是细胞形状的关键例子 在发育和生理过程中发生变化,而在癌症中, 黑素瘤细胞骨架的主动控制被认为是细胞形状变化的关键, 而同时发生的质膜重塑可能不太受重视。尽管许多 细胞骨架和膜重塑组分是已知的,并且它们的生物化学和结构 由于上述特征,我们缺乏对这些不同系统如何监管的系统性理解 并协调细胞形状的变化。也许细胞中最重要的问题 形态发生是理解细胞如何感知环境中的线索, 通过协调的细胞骨架动力学和质膜重塑将信息转化为形状变化。 小GTP酶和激酶的功能在调节细胞骨架动力学和膜 重塑我实验室的工作确定了E3泛素连接酶在调节细胞形状中的新作用 变化我们鉴定了两种E3泛素连接酶,TRIM 9和TRIM 67,它们调节细胞骨架和胞吐, 蛋白质和细胞形状的变化。Netrin是一种细胞外形态原, 神经元形态发生和癌症如黑色素瘤的进展。TRIM9和TRIM67因此 为实验室研究细胞骨架和膜重塑是如何 协调netrin触发的形态发生和运动。TRIM9和TRIM67共享相似的序列, 定位和相互作用伙伴,然而,我们的研究确定了这些相关蛋白质的不同功能 和与其缺失相关的拮抗表型。该计划的首要目标是测试 TRIM9和TRIM67协调netrin依赖性细胞骨架动力学和胞吐作用假说 神经元和迁移性黑素瘤细胞的形态发生。我们的工作将提供基本的机制 了解发育过程中细胞骨架和膜运输的调节, 转移

项目成果

期刊论文数量(0)
专著数量(0)
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会议论文数量(0)
专利数量(0)

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Stephanie Gupton其他文献

Stephanie Gupton的其他文献

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{{ truncateString('Stephanie Gupton', 18)}}的其他基金

Netrin Glycosylation Influences Chemotaxis and Haptotaxis
Netrin 糖基化影响趋化性和趋触性
  • 批准号:
    10665243
  • 财政年份:
    2023
  • 资助金额:
    $ 9万
  • 项目类别:
Exploring The Brain Enriched E3 Ubiquitin Ligase TRIM9 in Alzheimer's Disease
探索大脑富含 E3 泛素连接酶 TRIM9 在阿尔茨海默病中的作用
  • 批准号:
    10467201
  • 财政年份:
    2022
  • 资助金额:
    $ 9万
  • 项目类别:
Super Resolution STED Microscopy at UNC
北卡罗来纳大学超分辨率 STED 显微镜
  • 批准号:
    10414283
  • 财政年份:
    2022
  • 资助金额:
    $ 9万
  • 项目类别:
Coordinated Cytoskeletal Dynamics and Membrane Remodeling in Cellular Shape Change
细胞形状变化中协调的细胞骨架动力学和膜重塑
  • 批准号:
    10306344
  • 财政年份:
    2019
  • 资助金额:
    $ 9万
  • 项目类别:
Exocytosis fuels plasma membrane expansion in developing neurons
胞吐作用促进发育中神经元的质膜扩张
  • 批准号:
    10402882
  • 财政年份:
    2019
  • 资助金额:
    $ 9万
  • 项目类别:
Coordinated Cytoskeletal Dynamics and Membrane Remodeling in Cellular Shape Change
细胞形状变化中协调的细胞骨架动力学和膜重塑
  • 批准号:
    10063996
  • 财政年份:
    2019
  • 资助金额:
    $ 9万
  • 项目类别:
Exocytosis fuels plasma membrane expansion in developing neurons
胞吐作用促进发育中神经元的质膜扩张
  • 批准号:
    10159320
  • 财政年份:
    2019
  • 资助金额:
    $ 9万
  • 项目类别:
Supplement to Support Diversity in Research
支持研究多样性的补充
  • 批准号:
    10596422
  • 财政年份:
    2019
  • 资助金额:
    $ 9万
  • 项目类别:
Investigation of TRIM9 in cell shape change in the aging brain
TRIM9 在衰老大脑细胞形状变化中的研究
  • 批准号:
    10121328
  • 财政年份:
    2019
  • 资助金额:
    $ 9万
  • 项目类别:
Undergraduate Research: Coordinated Cytoskeletal Dynamics and Membrane Remodeling in Cellular Shape Change
本科生研究:细胞形状变化中的协调细胞骨架动力学和膜重塑
  • 批准号:
    10586656
  • 财政年份:
    2019
  • 资助金额:
    $ 9万
  • 项目类别:

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