Myopalladin’s role in cardiac muscle function and disease
Myopalladin 在心肌功能和疾病中的作用
基本信息
- 批准号:10581826
- 负责人:
- 金额:$ 2.21万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-09-01 至 2024-08-31
- 项目状态:已结题
- 来源:
- 关键词:ActinsAffectAgingArchitectureBindingBiochemicalBiochemistryBioinformaticsBiological AssayBiological ProcessBiologyBiomedical EngineeringBiophysicsC-terminalCardiacCardiomyopathiesCellsChemicalsCytoskeletonDISC componentsDataDevelopmentDiseaseDrosophila genusEducationF-ActinFamilyFluorescenceFutureGoalsGrowthHeartHeart AbnormalitiesHeart DiseasesHumanImmunoglobulin DomainIndustrial HealthInheritedKineticsKnowledgeLearningLengthLinkLiteratureMaintenanceMass Spectrum AnalysisMeasurementMeasuresMicrofilamentsMolecularMolecular BiologyMorphologyMuscleMuscle ProteinsMuscle functionMutationMyocardial dysfunctionMyocardiumMyopathyPathogenesisPhenotypePlayPreventionProcessPropertyProtein EngineeringProteinsPublishingRegulationResearchResearch InfrastructureRoleSarcomeresScientistSedimentation processSkeletal MuscleStructureStudentsTechniquesTestingThin FilamentUniversitiesWichitaWorkbasecrosslinkdepolymerizationdesignexperimental studygraduate studentin vivoinherited cardiomyopathyinnovationinsightinstrumentationinterdisciplinary curriculummechanical propertiesmultidisciplinarymutantmyopalladinnovelnovel therapeuticspolymerizationprogramsprotein functionprotein protein interactionprotein structure functionsingle moleculeundergraduate research experienceundergraduate student
项目摘要
Project Summary
Project Title: Myopalladin’s role in cardiac muscle function and disease
Decades of research have provided fundamental insight into the human heart’s structure and function.
Yet, most cardiac malformations remain a mystery as scientists and clinicians continue to examine how inherited
mutations and aging affect the normal biological functions of proteins associated with cardiac dysfunction.
Recently, mutations in the muscle protein myopalladin have been linked to the pathogenesis of three of the four
major types of cardiomyopathy. Myopalladin is thought to be involved in regulating the organization of sarcomere
structure, however insufficient knowledge of myopalladin’s interactions with other key molecules in the
sarcomere has hampered development of new therapies for cardiomyopathies and other debilitating muscle
diseases. Mutations in myopalladin cause diverse cardiomyopathic phenotypes that are poorly understood;
therefore, our goal is to uncover the molecular mechanisms and discover how sarcomere thin filament assembly
occurs.
Myopalladin and palladin belong to a family of closely related immunoglobulin (Ig)-domain-containing
proteins that have essential, but uncharacterized roles in organizing the actin cytoskeleton. Previous work in the
Beck lab revealed that palladin binds directly to actin and increases both the rate of actin polymerization and the
stability of actin filaments. Our more recent results indicate that myopalladin also binds and bundles filamentous
actin, however myopalladin reduced actin polymerization and strongly inhibits depolymerization. The fact that a
number of mutations in myopalladin are located within the analogous actin-binding region suggests that a
disruption in actin regulation may occur in cardiomyopathy. The objective of this application is to provide new
insights into the still largely elusive role of myopalladin in cardiac structure, function, and disease. We will
investigate the functional properties of myopalladin by employing multidisciplinary studies that integrate structural
and functional analysis of isolated proteins with characterization of actin assembly and sarcomere structure in
cultured and live cells. We will test our hypothesis that myopalladin promotes thin filament actin elongation by
examining interactions critical for this regulation that may also be disrupted by the cardiomyopathy-associated
mutations recently identified. Such studies will be a significant advance in our understanding of familial
cardiomyopathy and may motivate the development of new strategies to detect and treat cardiac disease.
项目摘要
项目名称:Myopalladin在心肌功能和疾病中的作用
几十年的研究为人类心脏的结构和功能提供了基本的见解。
然而,大多数心脏畸形仍然是一个谜,因为科学家和临床医生继续研究如何遗传
突变和衰老影响与心脏功能障碍相关的蛋白质的正常生物学功能。
最近,肌肉蛋白myopalladin的突变与四种中的三种的发病机制有关。
心肌病的主要类型Myopalladin被认为参与调节肌节的组织
然而,对myopalladin与其他关键分子的相互作用的了解不足,
肌节阻碍了心肌病和其他使肌肉衰弱的新疗法的发展,
疾病myopalladin的突变引起了各种心肌病表型,但这些表型的了解很少;
因此,我们的目标是揭示肌节细丝组装的分子机制,
发生。
Myopalladin和palladin属于一个密切相关的含有免疫球蛋白(IG)结构域的家族。
在组织肌动蛋白细胞骨架中具有基本但未表征的作用的蛋白质。以前的工作
Beck实验室揭示,palladin直接与肌动蛋白结合,并增加肌动蛋白聚合的速率和
肌动蛋白丝的稳定性。我们最近的研究结果表明,myopalladin也结合和捆绑丝状
肌动蛋白,然而,肌球蛋白减少肌动蛋白聚合和强烈抑制解聚。的事实
肌球蛋白中的一些突变位于类似的肌动蛋白结合区域内,这表明
心肌病中可能发生肌动蛋白调节的中断。本申请的目的是提供新的
对myopalladin在心脏结构,功能和疾病中仍然很难理解的作用的见解。我们将
通过采用整合结构的多学科研究来研究myopalladin的功能特性,
分离的蛋白质的功能分析,以及肌动蛋白组装和肌节结构的表征,
培养和活细胞。我们将检验我们的假设,即myopalladin促进细丝肌动蛋白的伸长,
检查对这种调节至关重要的相互作用,这种相互作用也可能被心肌病相关的
最近发现的突变。这些研究将是我们理解家族性疾病的一个重大进展。
心肌病,并可能激发新的战略,以检测和治疗心脏病的发展。
项目成果
期刊论文数量(0)
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{{ truncateString('MORIAH R BECK', 18)}}的其他基金
Myopalladin’s Role in Cardiac Muscle Function and Disease
Myopalladin 在心肌功能和疾病中的作用
- 批准号:
10292264 - 财政年份:2021
- 资助金额:
$ 2.21万 - 项目类别:
Myopalladin’s Role in Cardiac Muscle Function and Disease
Myopalladin 在心肌功能和疾病中的作用
- 批准号:
10606271 - 财政年份:2021
- 资助金额:
$ 2.21万 - 项目类别:
Probing Actin Filament Assembly, Structure, and Dynamics by Palladin
Palladin 探索肌动蛋白丝组装、结构和动力学
- 批准号:
9171290 - 财政年份:2016
- 资助金额:
$ 2.21万 - 项目类别:
Elucidating the role of palladin/alpha-actinin in cell motility and invasion
阐明 Palladin/α-肌动蛋白在细胞运动和侵袭中的作用
- 批准号:
7928090 - 财政年份:2009
- 资助金额:
$ 2.21万 - 项目类别:
Elucidating the role of palladin/alpha-actinin in cell motility and invasion
阐明 Palladin/α-肌动蛋白在细胞运动和侵袭中的作用
- 批准号:
7674257 - 财政年份:2009
- 资助金额:
$ 2.21万 - 项目类别:
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