Osiris Genes as Novel Coordinators of Protein Trafficking in Drosophila Trachea
Osiris 基因作为果蝇气管蛋白质运输的新协调者
基本信息
- 批准号:10291609
- 负责人:
- 金额:$ 43.9万
- 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:2021-07-01 至 2025-06-30
- 项目状态:未结题
- 来源:
- 关键词:ApicalAutophagosomeBindingBinding ProteinsBiologicalBiological AssayBiological ModelsBlood VesselsCessation of lifeCo-ImmunoprecipitationsCytoplasmic VesiclesDefectDepositionDiseaseDrosophila eyeDrosophila genusDrug Metabolic DetoxicationEndoplasmic ReticulumEndosomesEpithelialEpithelial CellsExtracellular MatrixGasesGene FamilyGenesGeneticGlycocalyxGlycolysisGoalsGolgi ApparatusHumanImageImmunohistochemistryIndividualInsectaInvertebratesKidneyKnowledgeLactoylglutathione LyaseLeadLifeLiquid substanceLungLysosomesMediatingMetabolicMorphogenesisMorphologyOrganOrganismPathway interactionsPhenotypePlayPolycystic Kidney DiseasesProcessPropertyProteinsPyruvaldehydeReportingRoleSequence HomologyShapesStructureSystemTestingTimeTracheaTubeTubular formationVascular DiseasesVertebratesVesicleYeastsbody systemexosomeexperimental studyextracellulargene functionhuman diseasein vivokidney vascular structuremalformationmembermonolayermutantnovelprotein transportsecretion processspine bone structuretrafficking
项目摘要
Summary
Biological tubes with appropriate sizes are critical for the proper functioning of most major human organ
systems (including but not limited to kidneys, lungs, and blood vessels). Malformation of tubes leads to various
human diseases, such as polycystic kidney disease and vascular diseases. Drosophila trachea is the premier
system to study the fundamental mechanisms underlying tubular organ formation.
The Drosophila trachea is a ramifying network of epithelial tubes with a monolayer of epithelial cells
surrounding an apical lumen. During tube expansion, the apical secretion burst deposits large amounts of
luminal matrix components to the apical extracellular lumen. This process is critical for tube expansion to
acquire mature sizes. Previous studies on apical secretion focused on the identification of components of the
vesicular trafficking pathway involved in this process. As expected, in addition to endoplasmic reticulum and
Golgi, a few endosomes are also required in this process. Instead of identifying additional trafficking
components, the objective of this project is to reveal the “broader coordination” of various trafficking
components during apical secretion. This is a previously underappreciated mechanism in apical secretion in
Drosophila trachea as well as in the overall field of vesicular trafficking.
Our preliminary study on a poorly understood Osiris (Osi) gene family strongly indicates that Osi family
genes function as “traffic coordinators” to direct post-Golgi protein trafficking. In addition, a recent homology
search revealed that Osi genes share noticeable sequence homology to glyoxalase 1 (Glo-1). Glo-1 is well
known for its function in detoxification of methylglyoxal, a metabolic byproduct of glycolysis. It has been
reported that Glo-1 plays a role in vesicular trafficking as well as morphological changes in blood vessels.
These discoveries lead to a plausible hypothesis that they may also have some functional overlap in tubular
organs. Our central hypothesis is that Osi genes function as “traffic coordinators” to direct apical proteins by
coordinated changes within secretion-related (e.g. endosomes, exosomes) and degradation-related trafficking
components (e.g. lysosomes, autophagosomes). We will test this hypothesis by completing the following three
specific aims: Aim. 1 Determine the function of Osi genes in apical secretion of the apical luminal matrix during
tube expansion. Aim. 2: Determine the function of Osi genes as coordinators to increase numbers, volumes,
activities of secretion-related trafficking components at the expense of degradation-related trafficking
components in trachea. Aim. 3: Identify proteins that directly bind to Osi proteins.
This project is significant because understanding the “broader coordination” between various trafficking
components will fill the gap in our understanding of the regulatory hierarchy in protein trafficking.
总结
具有适当尺寸的生物管对于大多数主要人体器官的正常功能至关重要
系统(包括但不限于肾脏、肺和血管)。管畸形导致各种
人类疾病,如多囊肾病和血管疾病。果蝇气管是第一个
系统研究管状器官形成的基本机制。
果蝇气管是一个由单层上皮细胞组成的上皮管分支网络
围绕着顶端腔。在输卵管扩张期间,顶端分泌物爆发沉积大量的
腔基质成分的顶端细胞外腔。该过程对于管膨胀至关重要,
获得成熟的尺寸。以前对根尖分泌的研究主要集中在鉴定根尖分泌物的成分上。
囊泡运输途径参与这一过程。正如所料,除了内质网和
高尔基体,一些内体也需要在这个过程中。而不是查明更多的贩运活动
该项目的目标是揭示各种贩运活动的“更广泛的协调”,
成分在顶端分泌。这是以前未被充分认识的顶分泌机制,
果蝇的气管以及整个领域的囊泡贩运。
我们对一个鲜为人知的Osiris(Osi)基因家族的初步研究表明,Osi家族
基因作为“交通协调员”来指导高尔基体后蛋白质的运输。此外,最近的一个同源
检索显示Osi基因与glycoprotein酶1(Glo-1)具有显著的序列同源性。Glo-1很好
已知其在解毒甲基乙二醛(糖酵解的代谢副产物)中的功能。已经
报道Glo-1在囊泡运输以及血管的形态变化中起作用。
这些发现导致了一个合理的假设,即它们在肾小管中也可能有一些功能重叠。
机关我们的中心假设是,Osi基因作为“交通协调员”,
分泌相关(例如内体、外泌体)和降解相关运输内的协调变化
组分(例如溶酶体、自噬体)。我们将通过完成以下三个测试来验证这一假设
具体目标:目标。1确定Osi基因在顶腔基质的顶端分泌中的功能,
胀管瞄准2:确定Osi基因作为协调者的功能,以增加数量,体积,
与分泌物相关的贩运成分的活动以牺牲与退化相关的贩运为代价
气管中的成分。瞄准3:鉴定直接与Osi蛋白结合的蛋白质。
该项目意义重大,因为了解各种贩运之间的“更广泛协调”
组分将填补我们对蛋白质运输中的调节层次结构的理解中的差距。
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)
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Lan Jiang其他文献
Lan Jiang的其他文献
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{{ truncateString('Lan Jiang', 18)}}的其他基金
Acquisition of an Olympus SZX7 fluorescent stereo microscope for dissecting late-stage Drosophila embryos and selecting Drosophila embryos with GFP/RFP tagged genes
获取奥林巴斯 SZX7 荧光体视显微镜,用于解剖晚期果蝇胚胎并选择带有 GFP/RFP 标记基因的果蝇胚胎
- 批准号:
10795289 - 财政年份:2021
- 资助金额:
$ 43.9万 - 项目类别:
Acquisition of a Drosophila chamber for culturing Drosophila strains
获得用于培养果蝇菌株的果蝇室
- 批准号:
10580919 - 财政年份:2021
- 资助金额:
$ 43.9万 - 项目类别:
The Drosophila expansion Gene Controls Tracheal Tube Diameter
果蝇扩张基因控制气管管直径
- 批准号:
8433039 - 财政年份:2013
- 资助金额:
$ 43.9万 - 项目类别:
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