Investigating the role of a novel non muscle myosin II network in apical domain organization of enterocytes
研究新型非肌肉肌球蛋白 II 网络在肠上皮细胞顶端域组织中的作用
基本信息
- 批准号:9911150
- 负责人:
- 金额:$ 3.02万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-03-01 至 2021-11-30
- 项目状态:已结题
- 来源:
- 关键词:ActinsAntibodiesApicalArchitectureBrush BorderCell Culture SystemCell Culture TechniquesCell surfaceCellsComplexCytoskeletonDataDevelopmentDiseaseDistalEnterocytesEpithelial CellsEukaryotic CellExhibitsFarming environmentFilamentFingersFunctional disorderGastrointestinal DiseasesGenesGrowthHeadImageIndividualInternetIntestinesInvestigationKineticsKnowledgeLeadLengthLigandsLightLightingLinkLocationLongevityMaintenanceMechanicsMembraneMicrofilamentsMicroscopyModelingMorphologyMotorMusMutationMyosin ATPaseMyosin Type IIN-terminalNonmuscle Myosin Type IIAOrganOrganismPerfusionPharmaceutical PreparationsPharmacotherapyPhosphotransferasesPlayPoint MutationPositioning AttributePreventionProcessProtein IsoformsProteinsResearchResolutionRoleS-nitro-N-acetylpenicillamineScanningSiteSmall IntestinesStainsStructureSurfaceSystemTailTestingThick FilamentTissuesbaseblebbistatincellular microvillusdimerexperimental studyfluorophoregastrointestinalgastrointestinal epitheliumgastrointestinal functioninhibitor/antagonistinsightintestinal epitheliumintestinal homeostasisknock-downnon-muscle myosinnovelnutrient absorptionoverexpressionpathogenregenerativeresponse
项目摘要
PROJECT SUMMARY
Within the intestine, nutrient absorption occurs at the brush border, a region of densely packed actin based
protrusions on the apical surface of enterocytes. These protrusions, known as microvilli, also form the first line
of defense against luminal pathogens. Proper formation of the brush border is dependent on the correct formation
and clustering of microvilli. Microvilli are membrane covered protrusions, each containing a bundle of 20-30 actin
filaments, with the plus ends located at the distal tips, and the minus ends anchored in a region of the cell known
as the terminal web. Enterocytes are continually being renewed, thus growth of microvilli is critical throughout
an organism’s entire lifespan. However, little is known about the mechanisms that drive the growth and
organization of microvilli, or the precise role of the terminal web.
Ultrastructural studies revealed many years ago that microvillar actin bundles are embedded in the dense
terminal web, although the composition and function of this structure remain ambiguous. Our preliminary studies
suggest that a major constituent of this structure is non-muscle myosin II (NMII), a filament-forming myosin motor
expressed in all eukaryotic cells. In the intestine, three different isoforms of NMII are expressed; A, B and C, with
NMII-A and NMII-C dominating expression in enterocytes. My preliminary super-resolution images reveal that
NMII-C forms a novel network across the enterocyte apical domain at the level of the terminal web. Line scans
along the microvillar axis show that NMII-C is enriched near the pointed-ends of microvillar actin bundles. In
preliminary studies using Blebbistatin, a myosin II inhibitor, native microvilli in mouse intestinal tissue get
noticeably shorter, and appear to lose their upright orientation relative the surface of the cell. Based on my
preliminary data, I hypothesize that a non-muscle myosin II network spanning the apical domain provides
necessary tension and mechanical support for microvillar growth and maintenance. To test this hypothesis, I will:
(Aim 1) define the organization of the sub-apical non-muscle myosin II network, and (Aim 2) determine the role
of NMII-C in the growth and organization of microvilli. Investigation of this novel myosin II array will significantly
deepen our understanding of the physical mechanisms of microvillar formation and maintenance, as well as
diseases linked to mutations in non-muscle myosin IIs.
项目总结
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 }}
Colbie Chinowsky其他文献
Colbie Chinowsky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 }}
相似海外基金
University of Aberdeen and Vertebrate Antibodies Limited KTP 23_24 R1
阿伯丁大学和脊椎动物抗体有限公司 KTP 23_24 R1
- 批准号:
10073243 - 财政年份:2024
- 资助金额:
$ 3.02万 - 项目类别:
Knowledge Transfer Partnership
Role of Natural Antibodies and B1 cells in Fibroproliferative Lung Disease
天然抗体和 B1 细胞在纤维增生性肺病中的作用
- 批准号:
10752129 - 财政年份:2024
- 资助金额:
$ 3.02万 - 项目类别:
CAREER: Next-generation protease inhibitor discovery with chemically diversified antibodies
职业:利用化学多样化的抗体发现下一代蛋白酶抑制剂
- 批准号:
2339201 - 财政年份:2024
- 资助金额:
$ 3.02万 - 项目类别:
Continuing Grant
Isolation and characterisation of monoclonal antibodies for the treatment or prevention of antibiotic resistant Acinetobacter baumannii infections
用于治疗或预防抗生素耐药鲍曼不动杆菌感染的单克隆抗体的分离和表征
- 批准号:
MR/Y008693/1 - 财政年份:2024
- 资助金额:
$ 3.02万 - 项目类别:
Research Grant
Discovery of novel nodal antibodies in the central nervous system demyelinating diseases and elucidation of the mechanisms through an optic nerve demyelination model
发现中枢神经系统脱髓鞘疾病中的新型节点抗体并通过视神经脱髓鞘模型阐明其机制
- 批准号:
23K14783 - 财政年份:2023
- 资助金额:
$ 3.02万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
Elucidation of the mechanisms controlling the physicochemical properties and functions of supercharged antibodies and development of their applications
阐明控制超电荷抗体的理化性质和功能的机制及其应用开发
- 批准号:
23KJ0394 - 财政年份:2023
- 资助金额:
$ 3.02万 - 项目类别:
Grant-in-Aid for JSPS Fellows
Developing first-in-class aggregation-specific antibodies for a severe genetic neurological disease
开发针对严重遗传神经系统疾病的一流聚集特异性抗体
- 批准号:
10076445 - 财政年份:2023
- 资助金额:
$ 3.02万 - 项目类别:
Grant for R&D
PLA2G2D Antibodies for Cancer Immunotherapy
用于癌症免疫治疗的 PLA2G2D 抗体
- 批准号:
10699504 - 财政年份:2023
- 资助金额:
$ 3.02万 - 项目类别:
Genetic adjuvants to elicit neutralizing antibodies against HIV
基因佐剂可引发抗艾滋病毒中和抗体
- 批准号:
10491642 - 财政年份:2023
- 资助金额:
$ 3.02万 - 项目类别:
Novel Immunogens to Elicit Broadly Cross-reactive Antibodies That Target the Hemagglutinin Head Trimer Interface
新型免疫原可引发针对血凝素头三聚体界面的广泛交叉反应抗体
- 批准号:
10782567 - 财政年份:2023
- 资助金额:
$ 3.02万 - 项目类别: