Geometry-dependent assembly of the septin cytoskeleton
septin 细胞骨架的几何依赖性组装
基本信息
- 批准号:9900831
- 负责人:
- 金额:$ 29.73万
- 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:2019-04-01 至 2023-03-31
- 项目状态:已结题
- 来源:
- 关键词:AffectAffinityAmino AcidsAtomic Force MicroscopyBacteriaBindingBiological AssayBiotinBullaCell ShapeCell membraneCell physiologyCellsCiliaComplexCytoskeletonDataDendritic SpinesDiffusionDiseaseFilamentFlagellaFluorescenceGeometryGoalsInfertilityKineticsLabelLearningLengthLinkLipid BilayersLocationMalignant NeoplasmsMass Spectrum AnalysisMeasuresMembraneModelingMolecular GeneticsMonitorNeuropathyNormal CellPathogenesisPolymersProcessProtein FamilyProteinsProteomicsRadialResolutionRodRoleShapesSignal TransductionSignaling ProteinSiteSpeedSurfaceWorkautism spectrum disorderbasebiophysical propertiescell cortexdensityexperimental studyflexibilityhuman diseaseimaging approachlink proteinmicrobialnanometerphysical modelpolymerizationrecruitresponsescaffoldsingle molecule
项目摘要
Summary/abstract Cell shape is integral to function and can be described in terms of plasma
membrane curvature. Many changes in cell curvature occur on the micrometer scale but
proteins are nanometers in size, raising the question as to how cells can perceive, control and
use micrometer-scale geometry. The septins are a conserved, filament-forming family of
proteins that preferentially assemble at sites of micrometer-scale membrane curvature. Septins
assemble on many curved surfaces including at the cytokinetic furrow, dendritic spines,
membrane blebs, around intracellular bacteria and bases of cilia and flagella. Given these
diverse cell contexts, malfunction of septins is linked to diverse human diseases including
many cancers, neuropathies and infertility. At sites of micrometer-scale membrane curvature,
septins can influence the diffusion of proteins in the membrane, act as scaffolds to bring
together signaling proteins, and impact the rigidity of the cell cortex. How curved septin
assemblies form and recruit signaling proteins to the local membrane is critical to understand
how septins link cell geometry to responses. Septin filament assembly occurs through
annealing of short (~24-32nm) oligomeric rods on lipid bilayers or other cytoskeletal networks.
We hypothesize that cells modulate the membrane affinity, length, density, and geometrical
arrangement of septins in a curvature-dependent manner. The goal of this proposal is to
identify the mechanisms directing assembly of septins on curved surfaces and to measure how
curved assemblies regulate signaling networks. We will combine a variety of imaging
approaches including high-resolution fluorescence, SEM and high-speed atomic force
microscopy (HS-AFM), modeling, proteomics, and molecular genetics. Based on preliminary
data, we hypothesize that curvature-dependent septin assembly involves mechanisms at work
on several length scales. This work will be directed by three aims: (1) Analyze septin
membrane interaction in curvature sensing; (2) Determine the biophysical properties of septin
filaments that enable curvature sensing; (3) Identify how curved septin assemblies recruit
specific signaling proteins. From the proposed experiments, we will learn how nanometer
length scale mechanisms contribute to the emergent mesoscale process of sensing micron-
scale curvature. These studies will also reveal how septin scaffolding may change as a
function of local curvature. The long-term goal of this proposed study is to identify how
septins recognize micrometer-scale curvature and then use shape information to modulate
cellular functions.
细胞形态与功能密切相关,可以用血浆来描述
膜曲率细胞曲率的许多变化发生在微米尺度上,
蛋白质是纳米级的,这就提出了细胞如何感知、控制和
使用微米级的几何形状。septins是一个保守的,形成细胞毒性的家族,
这些蛋白质优先聚集在微米级膜曲率的位点。Septins
聚集在许多弯曲的表面上,包括在细胞动力学沟,树突棘,
膜泡,围绕细胞内细菌和纤毛和鞭毛的基部。鉴于这些
不同的细胞环境,septins的功能障碍与多种人类疾病有关,包括
许多癌症、神经病和不育症。在微米级膜弯曲的部位,
septins可以影响蛋白质在膜中的扩散,作为支架,
信号蛋白,并影响细胞皮层的硬度。如何弯曲隔垫
组装形成并将信号蛋白募集到局部膜上对于理解
分隔符如何将单元格几何形状与响应关联起来。隔蛋白丝组装发生在
脂质双层或其他细胞骨架网络上的短(~24- 32 nm)寡聚体棒的退火。
我们假设细胞调节膜亲和力、长度、密度和几何形状,
以曲率依赖的方式排列隔片。本提案的目的是
识别引导在曲面上组装隔片的机制,并测量
弯曲的组件调节信号网络。我们将联合收割机
包括高分辨率荧光、扫描电镜和高速原子力的方法
显微镜(HS-AFM),建模,蛋白质组学和分子遗传学。根据初步
根据数据,我们假设曲率依赖性隔蛋白组装涉及工作机制
在几个长度尺度上。本文的工作有三个目的:(1)分析分离素
曲率传感中的膜相互作用;(2)确定Septin的生物物理性质
(3)确定弯曲的分隔蛋白组件如何招募
特异性信号蛋白从拟议的实验,我们将了解如何纳米
长度尺度机制有助于感应微米-
尺度曲率这些研究还将揭示septin支架可能如何变化,
局部曲率函数这项拟议研究的长期目标是确定如何
septins识别微米级曲率,然后使用形状信息进行调制,
细胞功能。
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 }}
Amy Susanne Gladfelter其他文献
Amy Susanne Gladfelter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('Amy Susanne Gladfelter', 18)}}的其他基金
Geometry-dependent assembly of the septin cytoskeleton
septin 细胞骨架的几何依赖性组装
- 批准号:
10379448 - 财政年份:2019
- 资助金额:
$ 29.73万 - 项目类别:
Cellular and Molecular Fungal Biology Gordon Research Conference
细胞和分子真菌生物学戈登研究会议
- 批准号:
9193149 - 财政年份:2016
- 资助金额:
$ 29.73万 - 项目类别:
TIRFM-imaging system for in vitro and in vivo cell biology
用于体外和体内细胞生物学的 TIRFM 成像系统
- 批准号:
8639757 - 财政年份:2014
- 资助金额:
$ 29.73万 - 项目类别:
Cytoplasmic organization by phase separations_Res1
通过相分离进行细胞质组织_Res1
- 批准号:
9306163 - 财政年份:2010
- 资助金额:
$ 29.73万 - 项目类别:
Cytoplasmic organization by phase separations_Res1
通过相分离进行细胞质组织_Res1
- 批准号:
9104868 - 财政年份:2010
- 资助金额:
$ 29.73万 - 项目类别:
相似海外基金
Construction of affinity sensors using high-speed oscillation of nanomaterials
利用纳米材料高速振荡构建亲和传感器
- 批准号:
23H01982 - 财政年份:2023
- 资助金额:
$ 29.73万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Affinity evaluation for development of polymer nanocomposites with high thermal conductivity and interfacial molecular design
高导热率聚合物纳米复合材料开发和界面分子设计的亲和力评估
- 批准号:
23KJ0116 - 财政年份:2023
- 资助金额:
$ 29.73万 - 项目类别:
Grant-in-Aid for JSPS Fellows
Development of High-Affinity and Selective Ligands as a Pharmacological Tool for the Dopamine D4 Receptor (D4R) Subtype Variants
开发高亲和力和选择性配体作为多巴胺 D4 受体 (D4R) 亚型变体的药理学工具
- 批准号:
10682794 - 财政年份:2023
- 资助金额:
$ 29.73万 - 项目类别:
Platform for the High Throughput Generation and Validation of Affinity Reagents
用于高通量生成和亲和试剂验证的平台
- 批准号:
10598276 - 财政年份:2023
- 资助金额:
$ 29.73万 - 项目类别:
Collaborative Research: DESIGN: Co-creation of affinity groups to facilitate diverse & inclusive ornithological societies
合作研究:设计:共同创建亲和团体以促进多元化
- 批准号:
2233343 - 财政年份:2023
- 资助金额:
$ 29.73万 - 项目类别:
Standard Grant
Collaborative Research: DESIGN: Co-creation of affinity groups to facilitate diverse & inclusive ornithological societies
合作研究:设计:共同创建亲和团体以促进多元化
- 批准号:
2233342 - 财政年份:2023
- 资助金额:
$ 29.73万 - 项目类别:
Standard Grant
Molecular mechanisms underlying high-affinity and isotype switched antibody responses
高亲和力和同种型转换抗体反应的分子机制
- 批准号:
479363 - 财政年份:2023
- 资助金额:
$ 29.73万 - 项目类别:
Operating Grants
Deconstructed T cell antigen recognition: Separation of affinity from bond lifetime
解构 T 细胞抗原识别:亲和力与键寿命的分离
- 批准号:
10681989 - 财政年份:2023
- 资助金额:
$ 29.73万 - 项目类别:
CAREER: Engineered Affinity-Based Biomaterials for Harnessing the Stem Cell Secretome
职业:基于亲和力的工程生物材料用于利用干细胞分泌组
- 批准号:
2237240 - 财政年份:2023
- 资助金额:
$ 29.73万 - 项目类别:
Continuing Grant
ADVANCE Partnership: Leveraging Intersectionality and Engineering Affinity groups in Industrial Engineering and Operations Research (LINEAGE)
ADVANCE 合作伙伴关系:利用工业工程和运筹学 (LINEAGE) 领域的交叉性和工程亲和力团体
- 批准号:
2305592 - 财政年份:2023
- 资助金额:
$ 29.73万 - 项目类别:
Continuing Grant