Control of cell ratcheting engagement during epithelial morphogenesis
Control of cell ratcheting engagement during epithelial morphogenesis
批准号:
10544507
负责人:
James Todd Blankenship
金额:
$29.49万
依托单位国家:
美国
项目类别:
财政年份:
2022
资助国家:
美国
项目状态:
未结题
起止时间:
2022-01-01 至 2025-12-31
关键词:
ActomyosinAdoptedAdultApicalAreaBehaviorBindingBiochemicalBiologicalBiological AssayCell AgingCell ShapeCell membraneCell physiologyCell surfaceCellsContractsCoupledCuesCytoskeletonDataData AnalysesDevelopmentDimensionsDrosophila genomeDrosophila genusEmbryoEpithelial CellsEpitheliumFRAP1 geneFrequenciesGenerationsGoalsImageIndividualIntentionIntercalated CellLipidsMass Spectrum AnalysisMeasurementMeasuresMembraneMesodermMitochondriaMorphogenesisMorphologyNaturePH DomainPIK3CG genePathway interactionsPatternPeriodicalsPeriodicityPhasePhosphatidylinositol PhosphatesPhosphatidylinositolsPhosphotransferasesPhysiologic pulsePopulationProcessProteinsProteomicsProto-Oncogene Proteins c-aktReportingSignal PathwaySignal TransductionSurfaceSystemTestingTissuesTubular formationWorkcell cortexcell motilityconstrictioncourse developmentgastrulationin vivoinsightinterfacialmTOR proteinnovelphosphatidylinositol 3,4,5-triphosphateprotein functionrecruitwound healing
中文摘要
项目摘要
上皮组织中的力产生通常是脉动的,肌动球蛋白网络产生高张力
在周期性分解之前细胞皮层的收缩力。这种细胞骨架力的脉冲性质
这意味着必须有细胞过程来提取单向变化,
细胞形状的变化。在以前的工作中(朱厄特等人,2017; Miao等人,2019年,我们发现,
细胞骨架力的产生与质膜的内吞重塑通过Sbf-
Rab 35管状隔室功能,以稳定收缩的细胞表面并允许细胞收缩
顶端(顶端收缩)或细胞界面(细胞嵌入)。然而,这种膜状细胞是如何
棘齿在特定细胞表面的接合仍然不清楚。在建议的研究中,我们会
检查参与棘轮效应的信息信号,并指导Sbf/Rab 35房室行为,
收缩界面或细胞顶点,并确定振荡持续时间,振幅,
频率和/或方向性,导致收缩持续性。我们的初步数据表明PIP 3是
这是逐步接触的一个关键决定因素--通过我们拟议的工作,我们将执行第一个
磷脂酰肌醇磷酸(PIP)在提供脂基膜线索中的表征
果蝇早期胚胎的形态发生和原肠胚形成/棘轮动力学。在第一个目标中,我们将
还分析了如何质膜超微结构是由棘轮过程重塑,并确定是否
PIP水平的发展模式,以驱动顶端收缩在中胚层侵入。我们的项目
然后转向系统识别Sbf和Rab 35蛋白伴侣在指导棘轮作用中的作用
参与,并检查细胞信号传导途径,指导收缩力的“切换”行为
从顶端表面到细胞界面的生成。我们的数据表明,在没有JAK/STAT的情况下,
信号,Sbf-Rab 35棘齿在胚胎中的所有顶端表面上接合,导致全球性的
顶端扁平和缢缩。此外,我们的研究将确定较大的Upd-JAK-STAT-Pi 3 K-PIP 3-Sbf-
Rab 35通路或两个独立的通路(PIP 3和JAK/STAT)是否协调调节
棘轮啮合。我们还应用了一种新的基于计算相位的密切圆方法来检测
收缩和膨胀位移的活跃期。最后,我们正在开发一种新的线粒体标记异位
再定位测定作为体内募集因子“充分性”的量度,并检查Akt/mTOR是否在细胞内表达。
Akt/mTOR通路调节细胞棘轮效应,可能证明了Akt/mTOR在细胞凋亡中的一种新的、高度新颖的功能。
控制上皮细胞的拓扑结构因此,计划中的项目有可能阐明一个大的,监管的
引导上皮组织中细胞棘轮作用的机制的层次。
英文摘要
Project Summary
Force generation in epithelial tissues is often pulsatile, with actomyosin networks generating high-tension
contractile forces at the cell cortex before cyclically disassembling. This pulsed nature of cytoskeletal forces
implies that there must be cellular processes to extract unidirectional changes that drive processive
transformations in cell shape. In previous work (Jewett et al., 2017; Miao et al., 2019), we found that
cytoskeletal force generation is coordinated with endocytic remodeling of the plasma membrane through Sbf-
Rab35 tubular compartmental function to stabilize contracted cell surfaces and permit the shrinking of cell
apices (apical constriction) or cell interfaces (cell intercalation). However, how this membranous cellular
ratchet becomes engaged at particular cell surfaces remains unclear. In the proposed studies, we will
examine the informational signals that engage ratcheting and direct Sbf/Rab35 compartmental behaviors to
contracting interfaces or cell apices, and identify the fundamental changes in oscillatory durations, amplitudes,
frequencies, and/or directionality that lead to contractile processivity. Our preliminary data indicates the PIP3 is
a critical determinant for ratcheting engagement – through our proposed work we will perform the first
characterization of phosphatidylinositol phosphates (PIPs) in providing lipid-based membrane cues for
morphogenesis and gastrulation/ratcheting dynamics in the early Drosophila embryo. In the first aim, we will
also analyze how the plasma membrane ultrastructure is remodeled by ratcheting processes and determine if
PIP levels are developmentally patterned to drive apical constriction during mesoderm ingression. Our project
then moves to a systematic identification of Sbf and Rab35 protein partners in directing ratcheting
engagement, and examines the cell signaling pathways that direct a “switching” behavior of contractile force
generation from the apical surface to cell interfaces. Our data indicates that, in the absence of JAK/STAT
signaling, the Sbf-Rab35 ratchet becomes engaged on all apical surfaces in the embryo, resulting in global
apical flattening and constriction. Further, our studies will define if a larger Upd-JAK-STAT-Pi3K-PIP3-Sbf-
Rab35 pathway or if two independent pathways (PIP3 and JAK/STAT) have been coordinated to regulate
ratcheting engagement. We also apply a new computational phase-based osculating circle approach to detect
active periods of contraction and expansion displacements. Finally, we are developing a new mito-tag ectopic
relocalization assay as a measure of “sufficiency” of recruiting factors in vivo, and examine if the Akt/mTOR
pathway regulates cell ratcheting, potentially demonstrating a new, highly novel function of Akt/mTOR in
controlling epithelial cell topologies. Thus, the planned project has the potential to elucidate a large, regulatory
hierarchy of the mechanisms that guide engagement of cell ratcheting in epithelial tissues.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
Volumetric analysis of epithelial morphogenesis with high spatiotemporal resolution
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批准号:10586534
-
项目类别:
-
资助金额:$29.49万
-
财政年份:2023
-
负责人:James Todd Blankenship
-
依托单位:
Control of cell ratcheting engagement during epithelial morphogenesis
-
批准号:10366809
-
项目类别:
-
资助金额:$29.49万
-
财政年份:2022
-
负责人:James Todd Blankenship
-
依托单位:
Sliding vertex behaviors during epithelial morphogenesis and tissue elongation
-
批准号:9789335
-
项目类别:
-
资助金额:$29.49万
-
财政年份:2018
-
负责人:James Todd Blankenship
-
依托单位:
Sliding vertex behaviors during epithelial morphogenesis and tissue elongation
-
批准号:10245156
-
项目类别:
-
资助金额:$29.49万
-
财政年份:2018
-
负责人:James Todd Blankenship
-
依托单位:
Mechanisms of membrane ratcheting during cell intercalation
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批准号:9440874
-
项目类别:
-
资助金额:$43.99万
-
财政年份:2017
-
负责人:James Todd Blankenship
-
依托单位:
Dynamics of Epithelial Polarity Proteins and the Control of Tissue Architecture
-
批准号:8309149
-
项目类别:
-
资助金额:$30.52万
-
财政年份:2011
-
负责人:James Todd Blankenship
-
依托单位:
Dynamics of Epithelial Polarity Proteins and the Control of Tissue Architecture
-
批准号:8042519
-
项目类别:
-
资助金额:$26.53万
-
财政年份:2011
-
负责人:James Todd Blankenship
-
依托单位:
Dynamics of Epithelial Polarity Proteins and the Control of Tissue Architecture
-
批准号:8423865
-
项目类别:
-
资助金额:$2.63万
-
财政年份:2011
-
负责人:James Todd Blankenship
-
依托单位:
Dynamics of Epithelial Polarity Proteins and the Control of Tissue Architecture
-
批准号:8912482
-
项目类别:
-
资助金额:$26.53万
-
财政年份:2011
-
负责人:James Todd Blankenship
-
依托单位:
Dynamics of Epithelial Polarity Proteins and the Control of Tissue Architecture
-
批准号:8535168
-
项目类别:
-
资助金额:$27.06万
-
财政年份:2011
-
负责人:James Todd Blankenship
-
依托单位:
Dynamics of Epithelial Polarity Proteins and the Control of Tissue Architecture
-
批准号:8710253
-
项目类别:
-
资助金额:$26.53万
-
财政年份:2011
-
负责人:James Todd Blankenship
-
依托单位:
Dynamics of epithelial polarity proteins in Drosophila
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批准号:7712587
-
项目类别:
-
资助金额:$6.87万
-
财政年份:2009
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负责人:James Todd Blankenship
-
依托单位:
Dynamics of epithelial polarity proteins in Drosophila
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批准号:7920111
-
项目类别:
-
资助金额:$6.8万
-
财政年份:2009
-
负责人:James Todd Blankenship
-
依托单位:
海外基金