Mechanisms that maintain and remodel the sensory cilium
维持和重塑感觉纤毛的机制
基本信息
- 批准号:9889126
- 负责人:
- 金额:$ 25.43万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-04-01 至 2023-03-31
- 项目状态:已结题
- 来源:
- 关键词:AcuteAfferent NeuronsBehaviorBindingBiochemicalBiological AssayBlindnessCaenorhabditis elegansCarbon DioxideCell physiologyCell surfaceCellsCellular MembraneChronicCiliaCuesCyclic GMPDendritesDestinationsDevelopmentDifferentiation and GrowthDioxygenasesDiseaseDynein ATPaseEnzymesEsthesiaFluorescence MicroscopyFunctional disorderGenesGeneticGenetic ScreeningGenetic TranscriptionGolgi ApparatusGuanylate CyclaseHomologous GeneHypoxiaHypoxia Inducible FactorIn SituIntegral Membrane ProteinInvertebratesLeftLifeLightMeasurementMeasuresMediatingMembraneMetabolismMicrobeMicrotubulesModelingMolecularMotorMutationNematodaNeuronsOdorsOrganellesPathway interactionsPhotoreceptorsPhysiologicalProcessProteinsProteomeReproductionResolutionRetinal DegenerationRetinal DiseasesRetinal DystrophyRhodopsinRoleSecond Messenger SystemsSensorySignal TransductionSiteStimulusStressStructureSurfaceSystemTestingTransducersVertebrate PhotoreceptorsVesicleatrial natriuretic factor receptor Abasecell typedisease-causing mutationexperimental studyextracellularhypoxia inducible factor 1in vivonovelparticlephotoreceptor degenerationprogramsprotein transportreceptorrecruitresponsetooltraffickingvesicle transport
项目摘要
PROJECT SUMMARY
Sensory neurons concentrate and organize molecules used to detect environmental stimuli into cilia, which are
specialized microtubule-based structures on the cell surface that function as cellular antennas. The proteins
that constitute the machinery of sensory transduction are synthesized elsewhere and must be separated from
other cellular proteins and transported to the cilium. The importance of mechanisms that mediate trafficking of
proteins to the sensory cilium is illustrated by disease-causing mutations that disrupt this process. Mutations
that compromise ciliary trafficking of the photopigment rhodopsin or the enzyme guanylyl cyclase cause retinal
dystrophies marked by photoreceptor degeneration and, ultimately, blindness. Despite the importance of
protein trafficking to the cilium, its underlying molecular mechanisms remain poorly understood. We propose to
use chemosensory BAG neurons of the nematode C. elegans as a model for discovery of mechanisms that
select and transport cargo destined for the sensory cilium. Like vertebrate photoreceptor neurons, BAG
neurons use cyclic GMP as a second messenger for sensory transduction, and the enzymes and effectors that
control cyclic GMP signals and turn them into electrical signals are highly similar to those found in
photoreceptor neurons. Trafficking of proteins to BAG cilia can be measured in situ using high-resolution
fluorescence microscopy assays, and powerful genetic tools are available to acutely or chronically manipulate
specific molecular pathways in BAG neurons and determine their function in trafficking to the cilium.
Importantly, C. elegans permits discovery of novel factors that mediate ciliary trafficking through genetic
screens and biochemical approaches. We propose to use this powerful experimental system to (1) delineate a
molecular pathway that matches cargo destined for the sensory cilium with specific motors that will carry it
through the dendrite to its destination, and (2) determine how trafficking mechanisms are regulated by
physiological or developmental cues that trigger remodeling of the BAG cilium. These studies will advance
understanding of a cellular process that is essential for sensory neuron function and viability and will integrate
cellular trafficking mechanisms with physiological and developmental programs that impact sensory cilia in
vivo.
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)
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Niels Ringstad其他文献
Niels Ringstad的其他文献
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{{ truncateString('Niels Ringstad', 18)}}的其他基金
Molecular genetics of sensory modulation of motor programs
运动程序感觉调节的分子遗传学
- 批准号:
10810213 - 财政年份:2017
- 资助金额:
$ 25.43万 - 项目类别:
Molecular genetics of sensory modulation of motor programs
运动程序感觉调节的分子遗传学
- 批准号:
10414440 - 财政年份:2017
- 资助金额:
$ 25.43万 - 项目类别:
Molecular genetics of sensory modulation of motor programs
运动程序感觉调节的分子遗传学
- 批准号:
10799013 - 财政年份:2017
- 资助金额:
$ 25.43万 - 项目类别:
Molecular genetics of sensory modulation of motor programs
运动程序感觉调节的分子遗传学
- 批准号:
9277049 - 财政年份:2017
- 资助金额:
$ 25.43万 - 项目类别:
Molecular genetics of sensory modulation of motor programs
运动程序感觉调节的分子遗传学
- 批准号:
10246929 - 财政年份:2017
- 资助金额:
$ 25.43万 - 项目类别:
Toll-like receptor signaling in sensory neuron differentiation and function.
感觉神经元分化和功能中的 Toll 样受体信号传导。
- 批准号:
9066757 - 财政年份:2014
- 资助金额:
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Mechanisms of neuropeptide signaling in the modulation of a serotonergic synapse.
神经肽信号传导在血清素突触调节中的机制。
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8676595 - 财政年份:2013
- 资助金额:
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Mechanisms of neuropeptide signaling in the modulation of a serotonergic synapse
神经肽信号传导调节血清素突触的机制
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Mechanisms of neuropeptide signaling in the modulation of a serotonergic synapse
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8516060 - 财政年份:2011
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