Cytoskeletal Mechanisms of Endocytosis

胞吞作用的细胞骨架机制

基本信息

  • 批准号:
    9024118
  • 负责人:
  • 金额:
    $ 12.5万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2013
  • 资助国家:
    美国
  • 起止时间:
    2013-07-01 至 2016-05-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Communication with the environment is essential for survival and proper functionality of individual cells within an organism. One element of such communication is exchange of components between the intracellular and extracellular space. It includes two major processes, secretion and endocytosis, which are roughly equivalent to export and import, respectively, in the human world. This project will focus on the mechanisms of the major endocytic pathway, clathrin-mediated endocytosis (CME), by which cells take up exogenous molecules and cell surface components in a highly selective way. The key step of CME is the initial formation of an endocytic vesicle. This process consists of: (i) Assembly of the clathrin-based coat, a multiprotein scaffold recruiting the cargo and the endocytic machinery to the sites of endocytosis~ (ii) invagination of the coated plasma membrane to form a clathrin-coated pit~ (iii) elongation of the pit and constrictions of its neck t form a clathrin-coated bud~ (iv) scission of the bud neck to form an endocytic vesicle~ and (v) inward movement of the vesicle. All these processes are energetically unfavorable and require force-generating machinery to occur. The ongoing research on the mechanisms of CME increasingly points to the actin cytoskeleton as an important component of the molecular machinery driving endocytic vesicle internalization. However, an explicit model for the specific roles of actin cytoskeleton in CME has not been formulated because of a lack of high resolution structural information about the cytoskeletal architecture at endocytic sites. The major reasons for this deficiency are an extremely small size and transient nature of actin patches associated with the endocytic sites, dense packing of individual actin filaments within these patche making them irresolvable by light microscopy, and a well-known difficulty of preserving dynamic actin filament networks for electron microscopy. Using our special expertise in platinum replica electron microscopy that is most useful for the analysis of the cytoskeletal architecture, we propose to determine the structural organization and molecular composition of actin filament arrays associated with various types of clathrin-coated structures, to correlate the changes in the cytoskeleton organization with different stages of formation and maturation of clathrin-coated structures, and establish roles of several key proteins in this process by functional approaches. By these studies, we will test a hypothesis that a branched actin network nucleated around the perimeter of a clathrin-coated pit exerts pushing force onto all three surfaces: the growing bud, the bud neck, and the plasma membrane at the base of a bud, in order to constrict and elongate the bud neck, but then it is rearranged into a comet tail that propels the newly formed vesicle into the cytoplasm. The results of these studies will significantly advance our understanding of the actin-dependent mechanisms of vesicle internalization during CME.
描述(由申请人提供):与环境的沟通对于生物体内单个细胞的生存和正常功能至关重要。这种通讯的一个要素是细胞内和细胞外空间之间的组分交换。 它包括两个主要的过程,分泌和内吞,在人类世界中分别大致相当于输出和输入。本项目将着重于主要的内吞途径,网格蛋白介导的内吞作用(CME)的机制,通过该机制,细胞以高度选择性的方式摄取外源分子和细胞表面成分。CME的关键步骤是内吞囊泡的初始形成。 该过程包括:(i)基于网格蛋白的涂层的组装,一种多蛋白支架,将货物和内吞机器募集到内吞位点~(ii)被膜的内陷形成被网格蛋白包被的小窝~(iii)小窝的伸长和颈部的收缩不形成被网格蛋白包被的芽~(iv)芽颈断裂形成内吞小泡;(v)小泡向内移动。所有这些过程在能量上都是不利的,需要力产生机制才能发生。目前对CME机制的研究越来越多地指出,肌动蛋白细胞骨架是驱动内吞囊泡内化的分子机制的重要组成部分。然而,一个明确的模型,肌动蛋白细胞骨架在CME的具体作用还没有制定,因为缺乏高分辨率的结构信息的细胞骨架结构的内吞网站。这种缺陷的主要原因是与内吞位点相关的肌动蛋白斑块的极小尺寸和瞬时性质,这些斑块内的单个肌动蛋白丝的致密包装使得它们通过光学显微镜无法分辨,以及众所周知的保存动态肌动蛋白丝网络用于电子显微镜的困难。 利用我们在铂复型电子显微镜方面的特殊专长,这对分析细胞骨架结构是最有用的,我们建议确定与各种类型的网格蛋白涂层结构相关的肌动蛋白丝阵列的结构组织和分子组成,以将细胞骨架结构与细胞骨架结构相关联。 在网格蛋白包被结构的形成和成熟的不同阶段的细胞骨架组织的变化,并建立几个关键蛋白在这一过程中的作用,通过功能的方法。通过这些研究,我们将检验一个假设,即围绕网格蛋白包被的小坑周边成核的分支肌动蛋白网络对细胞施加推力。 三个表面:生长中的芽、芽颈和芽基部的质膜,以便收缩和拉长芽颈,但随后它被重新排列成彗星尾,将新形成的小泡推进细胞质。 这些研究的结果将 显著推进我们对CME期间囊泡内化的肌动蛋白依赖机制的理解。

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 }}

Tatyana Svitkina其他文献

Tatyana Svitkina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('Tatyana Svitkina', 18)}}的其他基金

Structure and functions of the actin cytoskeleton
肌动蛋白细胞骨架的结构和功能
  • 批准号:
    10667325
  • 财政年份:
    2021
  • 资助金额:
    $ 12.5万
  • 项目类别:
Structure and functions of the actin cytoskeleton
肌动蛋白细胞骨架的结构和功能
  • 批准号:
    10470372
  • 财政年份:
    2021
  • 资助金额:
    $ 12.5万
  • 项目类别:
Structure and functions of the actin cytoskeleton
肌动蛋白细胞骨架的结构和功能
  • 批准号:
    10794592
  • 财政年份:
    2021
  • 资助金额:
    $ 12.5万
  • 项目类别:
Structure and functions of the actin cytoskeleton
肌动蛋白细胞骨架的结构和功能
  • 批准号:
    10165228
  • 财政年份:
    2021
  • 资助金额:
    $ 12.5万
  • 项目类别:
Cytoskeletal Mechanisms of Endocytosis
胞吞作用的细胞骨架机制
  • 批准号:
    9068275
  • 财政年份:
    2013
  • 资助金额:
    $ 12.5万
  • 项目类别:
Cytoskeletal Mechanisms of Endocytosis
胞吞作用的细胞骨架机制
  • 批准号:
    8689101
  • 财政年份:
    2013
  • 资助金额:
    $ 12.5万
  • 项目类别:
Cytoskeletal Mechanisms of Endocytosis
胞吞作用的细胞骨架机制
  • 批准号:
    8434606
  • 财政年份:
    2013
  • 资助金额:
    $ 12.5万
  • 项目类别:
Cytoskeletal Mechanisms of Endocytosis
胞吞作用的细胞骨架机制
  • 批准号:
    9272215
  • 财政年份:
    2013
  • 资助金额:
    $ 12.5万
  • 项目类别:
Multifaceted roles of nonmuscle myosin II in cell adhesion and migration
非肌肉肌球蛋白 II 在细胞粘附和迁移中的多方面作用
  • 批准号:
    9307035
  • 财政年份:
    2013
  • 资助金额:
    $ 12.5万
  • 项目类别:
Multifaceted roles of nonmuscle myosin II in cell adhesion and migration
非肌肉肌球蛋白 II 在细胞粘附和迁移中的多方面作用
  • 批准号:
    9891615
  • 财政年份:
    2013
  • 资助金额:
    $ 12.5万
  • 项目类别:

相似海外基金

Rational design of rapidly translatable, highly antigenic and novel recombinant immunogens to address deficiencies of current snakebite treatments
合理设计可快速翻译、高抗原性和新型重组免疫原,以解决当前蛇咬伤治疗的缺陷
  • 批准号:
    MR/S03398X/2
  • 财政年份:
    2024
  • 资助金额:
    $ 12.5万
  • 项目类别:
    Fellowship
CAREER: FEAST (Food Ecosystems And circularity for Sustainable Transformation) framework to address Hidden Hunger
职业:FEAST(食品生态系统和可持续转型循环)框架解决隐性饥饿
  • 批准号:
    2338423
  • 财政年份:
    2024
  • 资助金额:
    $ 12.5万
  • 项目类别:
    Continuing Grant
Re-thinking drug nanocrystals as highly loaded vectors to address key unmet therapeutic challenges
重新思考药物纳米晶体作为高负载载体以解决关键的未满足的治疗挑战
  • 批准号:
    EP/Y001486/1
  • 财政年份:
    2024
  • 资助金额:
    $ 12.5万
  • 项目类别:
    Research Grant
Metrology to address ion suppression in multimodal mass spectrometry imaging with application in oncology
计量学解决多模态质谱成像中的离子抑制问题及其在肿瘤学中的应用
  • 批准号:
    MR/X03657X/1
  • 财政年份:
    2024
  • 资助金额:
    $ 12.5万
  • 项目类别:
    Fellowship
CRII: SHF: A Novel Address Translation Architecture for Virtualized Clouds
CRII:SHF:一种用于虚拟化云的新型地址转换架构
  • 批准号:
    2348066
  • 财政年份:
    2024
  • 资助金额:
    $ 12.5万
  • 项目类别:
    Standard Grant
The Abundance Project: Enhancing Cultural & Green Inclusion in Social Prescribing in Southwest London to Address Ethnic Inequalities in Mental Health
丰富项目:增强文化
  • 批准号:
    AH/Z505481/1
  • 财政年份:
    2024
  • 资助金额:
    $ 12.5万
  • 项目类别:
    Research Grant
ERAMET - Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
ERAMET - 快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
  • 批准号:
    10107647
  • 财政年份:
    2024
  • 资助金额:
    $ 12.5万
  • 项目类别:
    EU-Funded
BIORETS: Convergence Research Experiences for Teachers in Synthetic and Systems Biology to Address Challenges in Food, Health, Energy, and Environment
BIORETS:合成和系统生物学教师的融合研究经验,以应对食品、健康、能源和环境方面的挑战
  • 批准号:
    2341402
  • 财政年份:
    2024
  • 资助金额:
    $ 12.5万
  • 项目类别:
    Standard Grant
Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
  • 批准号:
    10106221
  • 财政年份:
    2024
  • 资助金额:
    $ 12.5万
  • 项目类别:
    EU-Funded
Recite: Building Research by Communities to Address Inequities through Expression
背诵:社区开展研究,通过表达解决不平等问题
  • 批准号:
    AH/Z505341/1
  • 财政年份:
    2024
  • 资助金额:
    $ 12.5万
  • 项目类别:
    Research Grant
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了