Common Regulatory Pathways for the Genesis of Lysosome-Related Organelles and Dynamics of Microtubules during Development
溶酶体相关细胞器的起源和发育过程中微管动力学的常见调控途径
基本信息
- 批准号:10269015
- 负责人:
- 金额:$ 43.79万
- 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:2020-09-30 至 2025-08-31
- 项目状态:未结题
- 来源:
- 关键词:AffectAntigen-Presenting CellsBehaviorBiogenesisBiologicalBlastodermBlood PlateletsCHS1 geneCell NucleusCellsCentrosomeComaComplexCytoplasmCytoplasmic GranulesCytotoxic T-LymphocytesDefectDevelopmentDissociationDominant-Negative MutationDrosophila genusDynein ATPaseEmbryoEnabling FactorsEndosomesFailureFemaleFilmGenesGeneticHumanImmunologicsIn VitroKnowledgeLysosomesLyticMass Spectrum AnalysisMediatingMelanosomesMicrotubule-Associated ProteinsMicrotubulesMitosisModelingMolecularMothersMutateMutationOocytesOrganellesPathway interactionsPatientsPharmaceutical PreparationsPhenotypePilot ProjectsPolyploidyPositioning AttributeProcessProteinsRegulatory PathwayReportingResearchResolutionRoleSNAP receptorSystemTestingTranslatingVesiclecell typechediak-higashi syndromedelta proteindynactingamma Tubulingene productimmunological synapselysosomal proteinsmutantprotein transportrecruittherapeutic developmenttrafficking
项目摘要
PROJECT SUMMARY
Lysosome-Related Organelles (LROs) contain both lysosomal proteins and cell-type specific proteins
in an acidic lumen. They are enlarged in Chediak-Higashi Syndrome (CHS) patients resulting from
either excessive fusion or inhibition of their fission. The mutated gene in CHS encodes the lysosomal
trafficking regulator (LYST) protein, whose function is poorly understood. Defects in microtubule
behavior and centrosome behavior are seen at the immunological synapse of CHS patients but whether
microtubule nucleation is affected directly in CHS cells is controversial.
To determine LYST's function in LROs and clarify its requirements at microtubules, we will use a
Drosophila model in which mutants of the LYST counterpart, encoded by the mauve (mv) gene, show
enlarged LROs (yolk granules) and microtubule defects in mitosis and in maintaining nuclei at the
correct position in the embryo. Mauve co-immunoprecipitates from Drosophila embryos with factors
involved in maturation of endosomes; a factor enabling dissociation of the SNARE complex from
mature vesicles; Dynein/Dynactin, which have roles in vesicle trafficking and at microtubules; and
several centrosome-associated molecules. Thus, this stage of Drosophila development is highly
amenable to study the role of LYST/Mauve in the biogenesis of LROs and at microtubules and
centrosomes.
To establish the role of the Mauve/LYST complex in regulating LRO size and trafficking, we will follow yolk
granule biogenesis in wild-type and mv-mutant females; determine the effects of constitutively active and
dominant-negative forms of the enodcytotic regulators Rab5, Rab7 and NSF1. To discover the role of
Mauve/LYST complex in regulating microtubule dynamics, we will determine microtubule defects in mv-
derived embryos and establish the genetic interactions between mv and genes for microtubule associated
proteins with which it associates and physical interactions between these gene products. By determining
how Mauve directs the centrosomal association of Minispindles protein; how together with Rab5 and Dynein,
it promotes accumulation of microtubule associated proteins at the centrosome; and how Mauve's partner
proteins participate in recruitment of microtubule organizing molecules at centrosomes we will uncover how
vesicle trafficking associated proteins can participate in promoting centrosomal maturation.
We anticipate that this will define the dual role of Mauve/LYST in regulating vesicle fission/fusion and
in the trafficking of proteins important for microtubule nucleation and centrosome maturation. We
anticipate our findings will translate to human cells where they will have potential to unlock doors for the
development of therapeutic agents to treat the immunological defects of CHS patients.
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 }}
David M Glover其他文献
RNA interference by production of short hairpin dsRNA in ES cells, their differentiated derivatives, and in somatic cell lines.
通过在 ES 细胞、其分化衍生物和体细胞系中产生短发夹 dsRNA 进行 RNA 干扰。
- DOI:
- 发表时间:
2003 - 期刊:
- 影响因子:2.7
- 作者:
J. Grabarek;Florence Wianny;B. Płusa;Magdalena Zernicka;David M Glover - 通讯作者:
David M Glover
David M Glover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('David M Glover', 18)}}的其他基金
Generation of Diverse Centrosomes, Cilia and Flagellae During Development
发育过程中多种中心体、纤毛和鞭毛的产生
- 批准号:
10337138 - 财政年份:2020
- 资助金额:
$ 43.79万 - 项目类别:
Common Regulatory Pathways for the Genesis of Lysosome-Related Organelles and Dynamics of Microtubules during Development
溶酶体相关细胞器的起源和发育过程中微管动力学的常见调控途径
- 批准号:
10099427 - 财政年份:2020
- 资助金额:
$ 43.79万 - 项目类别:
Generation of diverse centrosomes, cilia and flagellae during development
发育过程中产生不同的中心体、纤毛和鞭毛
- 批准号:
10163281 - 财政年份:2020
- 资助金额:
$ 43.79万 - 项目类别:
Common Regulatory Pathways for the Genesis of Lysosome-Related Organelles and Dynamics of Microtubules during Development
溶酶体相关细胞器的起源和发育过程中微管动力学的常见调控途径
- 批准号:
10684931 - 财政年份:2020
- 资助金额:
$ 43.79万 - 项目类别:
Generation of Diverse Centrosomes, Cilia and Flagellae During Development
发育过程中多种中心体、纤毛和鞭毛的产生
- 批准号:
10590581 - 财政年份:2020
- 资助金额:
$ 43.79万 - 项目类别:
相似海外基金
Tri-Signal Artificial Antigen Presenting Cells for Cancer Immunotherapy
用于癌症免疫治疗的三信号人工抗原呈递细胞
- 批准号:
10751133 - 财政年份:2023
- 资助金额:
$ 43.79万 - 项目类别:
Microfluidic Precision Engineered Artificial Antigen Presenting Cells for Cancer Immunotherapy
用于癌症免疫治疗的微流控精密工程人工抗原呈递细胞
- 批准号:
10696138 - 财政年份:2022
- 资助金额:
$ 43.79万 - 项目类别:
The role of microglia as antigen presenting cells in Globoid Cell Leukodystrophy
小胶质细胞作为抗原呈递细胞在球状细胞脑白质营养不良中的作用
- 批准号:
10663066 - 财政年份:2022
- 资助金额:
$ 43.79万 - 项目类别:
The role of microglia as antigen presenting cells in Globoid Cell Leukodystrophy
小胶质细胞作为抗原呈递细胞在球状细胞脑白质营养不良中的作用
- 批准号:
10537159 - 财政年份:2022
- 资助金额:
$ 43.79万 - 项目类别:
Analysis of the function of antigen-presenting cells present in the stroma of colorectal cancer and the intracellular microbiome
结直肠癌基质中抗原呈递细胞和细胞内微生物组的功能分析
- 批准号:
21K08723 - 财政年份:2021
- 资助金额:
$ 43.79万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Class II artificial antigen presenting cells for cancer immunotherapy
用于癌症免疫治疗的 II 类人工抗原呈递细胞
- 批准号:
10156950 - 财政年份:2021
- 资助金额:
$ 43.79万 - 项目类别:
The role of CX3CR1+ antigen presenting cells in T cell selection and central tolerance"
CX3CR1抗原呈递细胞在T细胞选择和中枢耐受中的作用"
- 批准号:
10631854 - 财政年份:2021
- 资助金额:
$ 43.79万 - 项目类别:
Reprogramming Cancer Cells into Antigen Presenting Cells: Cancer Vaccination with mRNA Enabled by Charge-Altering Releasable Transporters
将癌细胞重编程为抗原呈递细胞:通过改变电荷的可释放转运蛋白实现 mRNA 的癌症疫苗接种
- 批准号:
10153927 - 财政年份:2021
- 资助金额:
$ 43.79万 - 项目类别:
Class II artificial antigen presenting cells for cancer immunotherapy
用于癌症免疫治疗的 II 类人工抗原呈递细胞
- 批准号:
10331830 - 财政年份:2021
- 资助金额:
$ 43.79万 - 项目类别:
Analysis on detrimental interplay between pathogenic helper T cells, inflammatory antigen-presenting cells and disease-associated microglia in chronic pathogenesis of multiple sclerosis
多发性硬化症慢性发病机制中致病性辅助 T 细胞、炎症抗原呈递细胞和疾病相关小胶质细胞之间的有害相互作用分析
- 批准号:
20K16294 - 财政年份:2020
- 资助金额:
$ 43.79万 - 项目类别:
Grant-in-Aid for Early-Career Scientists