Structure and Mechanics of Smooth Muscle Thin Filaments
Structure and Mechanics of Smooth Muscle Thin Filaments
批准号:
7329704
负责人:
WILLIAM J LEHMAN
金额:
$42.51万
依托单位国家:
美国
项目类别:
财政年份:
2007
资助国家:
美国
项目状态:
已结题
起止时间:
2007-07-01 至 2012-06-30
关键词:
Actin-Binding ProteinActininActinsAdaptor Signaling ProteinAffectAffinityAmino AcidsBehaviorBindingBinding SitesBlood PressureBlood VesselsBlood flowCardiovascular AgentsCell LineCell membraneCell physiologyCellsClassComplexConditionCoupledCrosslinkerCrystallographyCytoskeletal FilamentsCytoskeletal ProteinsCytoskeletonDataDiseaseDystrophinElectron MicroscopyElementsExtracellular MatrixF-ActinFilamentFluorescence MicroscopyGoalsHelix (Snails)Hot SpotHuman bodyHybridsIn SituIntermediate FilamentsLasersLeadLinkLocationLungMaintenanceMechanicsMethodsMicrofilamentsMicroscopicMolecularMolecular ConformationMolecular StructureMuscleMuscle RigidityNumbersOrganOrganellesOutcomePeptidesPhysiologicalPropertyProtein BindingProtein FamilyProteinsRangeResearch PersonnelResistanceResolutionRoleShapesSignaling ProteinSmooth MuscleSmooth Muscle Actin Staining MethodSmooth Muscle MyocytesSpectrinStructureTertiary Protein StructureTestingThin FilamentTransducersTropomyosinVascular SystemVisceralblood pressure regulationcaldesmoncalponincell preparationcrosslinkdensitydesignear helixexperienceintermolecular interactionmembermolecular domainmolecular rearrangementmonomeroptical trapsparticleplectinprogramsprotein Bprotein structurereconstructionstoichiometrytransmission process
中文摘要
肌动蛋白-细胞骨架是血管平滑肌细胞形状的主要决定因素
英文摘要
The actin-cytoskeleton is a major determinant of the shape of vascular smooth muscle cells and is proposed
to remodel during cell contraction and distension. Cytoskeletal remodeling requires the coordinated action of
actin binding proteins (ABPs) that stabilize, crosslink, cap and/or sever actin filaments. Under normal
physiological conditions the vascular system experiences a wide range of mechanical forces, and it is the
interactions of the cytoskeleton that enable vascular smooth muscle cells to sense and respond to
mechanical distension and compression (and any disease related alterations in these forces). The goal of
this proposal is to determine structural and mechanical effects of ABPs on the cytoskeleton of vascular
smooth muscle cells in order to understand the properties of this essential organelle. To elucidate the effects
of force on ABP binding as well as the effects of ABPs on cytoskeletal mechanics, information about the
molecular structure and mechanics of the single cytoskeletal microfilaments is required. Our approach will
take advantage of helical and single-particle analysis to define the location of ABP binding sites on actin,
thus revealing the potential for synergy or alternatively "parking problems" between ABPs on actin filaments.
In addition, we will fit atomic resolution structures into our reconstructions, thus pinpointing critical
intermolecular interactions between ABPs and actin. Since ABPs may alter both filament structure and
mechanics, the effects of ABP binding on actin flexural and torsional rigidity will be determined. Likewise, the
mechanical effect of force applied to F-actin on the binding of ABP to filaments will be assessed. These
structural and physical studies will characterize the molecular domains of ABPs that regulate cytoskeletal
dynamics and mechanical behavior. This information allows us to 1) define residues that are necessary for
cytoskeletal filaments to transmit and perceive forces and 2) design decoy peptides to be used by PPG
members to investigate physiological function in vascular cell preparations. Lay summary: Contraction and
the maintenance offeree by vascular smooth muscle cells that line blood vessels are key factors responsible
for controlling blood pressure and blood flow to the organs.of the human body. We will determine the
structure and mechanics of an intracellular skeleton composed of microscopic filaments, which control the
shape of vascular smooth muscle cells and hence help to regulate blood pressure and blood flow.
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Thin Filaments and Muscle Regulation
-
批准号:6690724
-
项目类别:
-
资助金额:$32.3万
-
财政年份:1986
-
负责人:WILLIAM J LEHMAN
-
依托单位:
Thin Filaments and Muscle Regulation
-
批准号:7998182
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项目类别:
-
资助金额:$40.63万
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财政年份:1986
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负责人:WILLIAM J LEHMAN
-
依托单位:
Thin Filaments and Muscle Regulation
-
批准号:8605902
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项目类别:
-
资助金额:$40.11万
-
财政年份:1986
-
负责人:WILLIAM J LEHMAN
-
依托单位:
Thin Filaments and Muscle Regulation
-
批准号:10355843
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项目类别:
-
资助金额:$41.25万
-
财政年份:1986
-
负责人:WILLIAM J LEHMAN
-
依托单位:
THIN FILAMENTS AND MUSCLE REGULATION
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批准号:2609240
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项目类别:
-
资助金额:$25.0万
-
财政年份:1986
-
负责人:WILLIAM J LEHMAN
-
依托单位:
THIN FILAMENTS AND VERTEBRATE SMOOTH MUSCLE CONTRACTION
-
批准号:3350869
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项目类别:
-
资助金额:$11.42万
-
财政年份:1986
-
负责人:WILLIAM J LEHMAN
-
依托单位:
THIN FILAMENTS AND MUSCLE REGULATION
-
批准号:2739330
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项目类别:
-
资助金额:$26.38万
-
财政年份:1986
-
负责人:WILLIAM J LEHMAN
-
依托单位:
Thin Filaments and Muscle Regulation
-
批准号:6819255
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项目类别:
-
资助金额:$32.3万
-
财政年份:1986
-
负责人:WILLIAM J LEHMAN
-
依托单位:
THIN FILAMENTS AND MUSCLE REGULATION
-
批准号:6330024
-
项目类别:
-
资助金额:$28.76万
-
财政年份:1986
-
负责人:WILLIAM J LEHMAN
-
依托单位:
Thin Filaments and Muscle Regulation
-
批准号:7735577
-
项目类别:
-
资助金额:$40.63万
-
财政年份:1986
-
负责人:WILLIAM J LEHMAN
-
依托单位:
Thin Filaments and Muscle Regulation
-
批准号:9184575
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项目类别:
-
资助金额:$40.93万
-
财政年份:1986
-
负责人:WILLIAM J LEHMAN
-
依托单位:
THIN FILAMENTS AND MUSCLE REGULATION
-
批准号:2218085
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项目类别:
-
资助金额:$22.38万
-
财政年份:1986
-
负责人:WILLIAM J LEHMAN
-
依托单位:
Thin Filaments and Muscle Regulation
-
批准号:6571367
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项目类别:
-
资助金额:$32.3万
-
财政年份:1986
-
负责人:WILLIAM J LEHMAN
-
依托单位:
THIN FILAMENTS AND VERTEBRATE SMOOTH MUSCLE CONTRACTION
-
批准号:3350870
-
项目类别:
-
资助金额:$12.38万
-
财政年份:1986
-
负责人:WILLIAM J LEHMAN
-
依托单位:
THIN FILAMENTS AND MUSCLE REGULATION
-
批准号:6476737
-
项目类别:
-
资助金额:$29.62万
-
财政年份:1986
-
负责人:WILLIAM J LEHMAN
-
依托单位:
THIN FILAMENTS AND MUSCLE REGULATION
-
批准号:6125751
-
项目类别:
-
资助金额:$27.92万
-
财政年份:1986
-
负责人:WILLIAM J LEHMAN
-
依托单位:
THIN FILAMENTS AND VERTEBRATE SMOOTH MUSCLE CONTRACTION
-
批准号:3350862
-
项目类别:
-
资助金额:$7.14万
-
财政年份:1986
-
负责人:WILLIAM J LEHMAN
-
依托单位:
THIN FILAMENTS AND VERTEBRATE SMOOTH MUSCLE CONTRACTION
-
批准号:3509914
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项目类别:
-
资助金额:$10.0万
-
财政年份:1986
-
负责人:WILLIAM J LEHMAN
-
依托单位:
Thin Filaments and Muscle Regulation
-
批准号:6986695
-
项目类别:
-
资助金额:$31.54万
-
财政年份:1986
-
负责人:WILLIAM J LEHMAN
-
依托单位:
THIN FILAMENTS AND MUSCLE REGULATION
-
批准号:2028238
-
项目类别:
-
资助金额:$24.04万
-
财政年份:1986
-
负责人:WILLIAM J LEHMAN
-
依托单位:
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