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The role of copines in the regulation of the actin cytoskeleton and membrane trafficking

The role of copines in the regulation of the actin cytoskeleton and membrane trafficking
脊髓灰质炎在肌动蛋白细胞骨架和膜运输调节中的作用
批准号:
10581990
负责人:
CYNTHIA K DAMER
金额:
$10.0万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2008
资助国家:
美国
项目状态:
未结题
起止时间:
2008-07-01 至 2025-03-31

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中文摘要
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英文摘要
PROJECT SUMMARY Copines are a family of calcium-dependent membrane binding proteins found in most eukaryotic organisms including humans, which have nine different copine genes. Copines have been implicated in numerous human cancers. However, at this time there is no unifying theme with respect to the function of these elusive proteins. The main goal of this research project is to determine whether a common basic mechanistic function can be attributed to all copine proteins. We have been using the model organism Dictyostelium discoideum to study these enigmatic proteins. Dictyostelium is a good model organism to study these proteins because they have six copines genes, while other model organisms either have a few or no copine genes. Our studies have mostly focused on Copine A (CpnA). However, we now have many of the tools to study the other five copines (CpnB-F). Our studies on cpnA knockout mutants in Dictyostelium indicate that CpnA is involved in many cellular functions including processes that require the actin cytoskeleton (i.e. cytokinesis, chemotaxis, cell polarity, and adhesion) and require membrane fusion (i.e. contractile vacuole expulsion, and postlysosome maturation and exocytosis). Biochemical studies indicate that CpnA binds to acidic phospholipids and actin filaments in a calcium-dependent manner. Localization studies indicate that CpnA is a soluble cytoplasmic protein that translocates to the plasma membrane and the membranes of the contractile vacuole system and organelles of the endolysosomal system in response to a rise in calcium concentration. Two main hypotheses for the function of CpnA emerge from our studies: CpnA functions in the calcium-dependent regulation of 1) actin filament dynamics and/or 2) membrane fusion. Therefore, we propose to use Dictyostelium to explore the idea that all copines, from single-celled organisms to humans, are involved in the calcium-dependent regulation of actin filament dynamics and/or membrane fusion. We plan to use several strategies that include the functional characterization of copine knockout mutants and identification of copine protein binding partners. Total Internal Reflection Fluorescence Microscopy (TIRF) will be used to visualize actin filament dynamics and membrane fusion in the copine knockout mutants. We will also explore the more specific hypothesis that copines regulate actin filaments on membrane surfaces to regulate membrane fusion. TIRF Microscopy is a special type of fluorescence microscopy that restricts excitation and emission of fluorophores to a very thin region of the specimen immediately adjacent to the glass coverslip and is used to image cellular processes happening close to the plasma membrane. If we find that not all copines function in the regulation of actin filament dynamics and/or membrane fusion, a unifying theme for copines will most likely emerge as we characterize each of the copine knockout mutants to identify any common defects and identify common binding-partners of copine proteins. This new knowledge can be then be used to understand the molecular mechanisms underlying many of the human cancers in which copines are highly expressed.
期刊论文(8)
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会议论文
Copine A regulates the size and exocytosis of contractile vacuoles and postlysosomes in Dictyostelium.
Copine A 调节盘基网柄菌中收缩液泡和后溶酶体的大小和胞吐作用。
DOI: 10.1002/2211-5463.12874
发表时间: 2020
期刊: FEBS open bio
影响因子: 2.6
作者: [Wight,EliseM, Ide,AmberD, Damer,CynthiaK]
通讯作者: Damer,CynthiaK
Copine A plays a role in the differentiation of stalk cells and the initiation of culmination in Dictyostelium development.
Copine A 在茎细胞的分化和盘基网柄菌发育高峰的启动中发挥作用。
DOI: 10.1186/1471-213x-10-59
发表时间: 2010
期刊: BMC developmental biology
影响因子: --
作者: [Smith,TashaS, Pineda,JaimieM, Donaghy,AlexC, Damer,CynthiaK]
通讯作者: Damer,CynthiaK
DOI: 10.1111/j.1440-169x.2011.01300.x
发表时间: 2011-10
期刊: Development, growth & differentiation
影响因子: --
作者: [Flegel KA, Pineda JM, Smith TS, Laszczyk AM, Price JM, Karasiewicz KM, Damer CK]
通讯作者: Damer CK
DOI: 10.1371/journal.pone.0250710
发表时间: 2021
期刊: PloS one
影响因子: 3.7
作者: [Ide AD, Wight EM, Damer CK]
通讯作者: Damer CK
Investigating of the Function of Copine A in Dictyostelium
  • 批准号:
    7515414
  • 项目类别:
  • 资助金额:
    $20.5万
  • 财政年份:
    2008
  • 负责人:
    CYNTHIA K DAMER
  • 依托单位:
The role of copines in the regulation of the actin cytoskeleton and membrane trafficking
  • 批准号:
    10203493
  • 项目类别:
  • 资助金额:
    $42.41万
  • 财政年份:
    2008
  • 负责人:
    CYNTHIA K DAMER
  • 依托单位:
Investigating of the Function of Copine A in Dictyostelium
  • 批准号:
    7801918
  • 项目类别:
  • 资助金额:
    $2.31万
  • 财政年份:
    2008
  • 负责人:
    CYNTHIA K DAMER
  • 依托单位:
CpnA's role in cAMP signaling and the actin cytoskeleton in Dictyostelium
  • 批准号:
    8434437
  • 项目类别:
  • 资助金额:
    $31.4万
  • 财政年份:
    2008
  • 负责人:
    CYNTHIA K DAMER
  • 依托单位:
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