Glial control of sensory neuron receptive-ending shape and function
神经胶质控制感觉神经元接受末端的形状和功能
基本信息
- 批准号:9239046
- 负责人:
- 金额:$ 37.08万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2016
- 资助国家:美国
- 起止时间:2016-12-01 至 2017-11-30
- 项目状态:已结题
- 来源:
- 关键词:ActinsAddressAffectAfferent NeuronsAnatomyAnimalsApoptoticAstrocytesBehaviorBindingBiological AssayBlindnessCaenorhabditis elegansCell ShapeCell physiologyCellsClinicalCuesCyclic GMPDendritic SpinesDependenceDevelopmentDiseaseGenesGenetic ScreeningGenetic studyGoalsGrowthGuanylate CyclaseHumanIonsLeadLearningLesionMammalsMediatingMemoryMicrogliaMolecularMolecular BiologyMorphogenesisMorphologyMotorMutationNematodaNervous System PhysiologyNervous system structureNeurogliaNeuronsOrganOrganismOutputPathologyPathway interactionsPatternPhosphatidylserinesPhotoreceptorsPhysiologyPlayProteinsRecruitment ActivityRegulationReportingRoleSchwann CellsSensoryShapesSignal PathwaySignal TransductionSiteSpecificityStimulusStructureStructure of retinal pigment epitheliumSynapsesTemperatureTemperature SenseTertiary Protein StructureTestingThrombospondin 1ThrombospondinsUsher SyndromeVertebral columnVertebratesVesiclecellular microvilluscongenital deafnessexperienceextracellularinherited retinal degenerationinhibitor/antagonistmutantnervous system disorderneurotransmissionnovelorgan growthoverexpressionphosphatidylserine receptorphotoreceptor cell outer segmentpostsynaptic neuronsprotein functionreceptorsynaptogenesisuptake
项目摘要
Our long-term goal is to understand glial control of neuron receptive-ending shape and function.
Neurons detect external stimuli through specialized dendritic receptive endings. Receptive-endings are
malleable and regulate neuronal output. For example, neurons receive information at dendritic spines.
Remodeling of spine shape occurs in development and is effected by experience. Perturbations in
spine shape are associated with neurological disorders, suggesting that spine morphogenesis may play
key roles in nervous system function. Like spines, receptive endings of sensory neurons are remodeled
in development and by experience. Photoreceptor cell outer segments, for example, are turned over
and rebuilt daily. Perturbation of sensory receptive-ending shape leads to sensory deficits and is a
common pathology in sensory diseases. Despite clear clinical importance, the questions of how
sensory cell shapes are regulated, how shape affects function, and how glia-neuron interactions control
sensory neuron receptive-ending shape, have not been extensively addressed. The nematode C.
elegans is an excellent organism in which to study glia-neuron interactions controlling sensory
receptive-ending morphogenesis and plasticity. Sensory organ anatomy, physiology, and molecular
biology are conserved from C. elegans to humans, making the nematode an exciting arena for
revealing general principles of sensory organ development and function. The C. elegans AFD neuron
mediates temperature sensation and cultivation-temperature memory. We showed that AFD receptive-
ending shape is dynamically controlled and uncovered a novel signaling pathway guiding these
changes. Shape changes require the receptor guanylyl cyclase GCY-8, controlling cGMP levels in AFD.
High cGMP blocks receptive-ending extension, and this is overcome by overexpression of the actin
regulator WASP-1. Loss of the glial transporter KCC-3, which specifically surrounds AFD, also blocks
microvilli growth, by removing Cl- ions from an extracellular microdomain around AFD. Cl- ions function
as novel direct inhibitors of GCY-8 cyclase activity. We further found that glia engulf and take up AFD
neuron receptive-ending fragments, and that engulfment is required for AFD neuron function. Our
results reveal glia-neuron interaction pathways determining neuron receptive-ending morphology,
components of which are conserved in mammals. We propose three aims: (1) We will determine how
glia form a unique microdomain around AFD neurons that is distinct from domains around other
neurons. (2) We will study the role of glial FIG-1/thrombospondin in engulfment of AFD receptive
endings and AFD neuron shape. (3) We will study the role of the phosphatidylserine receptor PSR-1 in
engulfment of AFD endings and shape.
我们的长期目标是了解神经胶质细胞对神经元感受器末端形状和功能的控制。
神经元通过专门的树突接受末梢检测外部刺激。感受性末梢是
可塑性和调节神经元输出。例如,神经元在树突棘上接收信息。
脊柱形态的重塑发生在发育过程中,并受经验的影响。中的扰动
脊柱的形状与神经系统疾病有关,这表明脊柱的形态发生可能
神经系统功能的关键角色。感觉神经元的感受性末梢和刺一样,
发展和经验。例如,感光细胞的外节
每天重建。感觉感受器末端形状的扰动导致感觉缺陷,
感觉疾病的常见病理学。尽管有明确的临床重要性,
感觉细胞的形状是受调节的,形状如何影响功能,以及神经胶质-神经元相互作用如何控制
感觉神经元感受器末端形状,还没有得到广泛的解决。线虫C.
线虫是研究神经胶质-神经元相互作用控制感觉神经元的极好生物体。
感受器末端形态发生和可塑性。感觉器官解剖学、生理学和分子生物学
生物学是从C.线虫对人类来说,使线虫成为一个令人兴奋的竞技场,
揭示了感觉器官发育和功能的一般原理。梭Elegans AFD神经元
介导温度感觉和培养温度记忆。我们发现渔农处接受-
末端形状是动态控制的,并揭示了一种新的信号通路,引导这些
变化形状变化需要受体鸟苷酸环化酶GCY-8,控制AFD中的cGMP水平。
高cGMP阻断受体末端的延伸,这是克服了过度表达的肌动蛋白
调节剂WASP-1。神经胶质转运蛋白KCC-3的缺失,特别是围绕AFD,也阻止了
微绒毛生长,通过从AFD周围的细胞外微区去除Cl-离子。氯离子功能
作为GCY-8环化酶活性的新型直接抑制剂。我们进一步发现胶质细胞吞噬并吸收AFD
神经元感受性末端片段,并且吞噬是AFD神经元功能所需的。我们
结果揭示了决定神经元感受器末端形态的胶质-神经元相互作用途径,
其组分在哺乳动物中是保守的。我们提出三个目标:(1)我们将确定如何
胶质细胞在AFD神经元周围形成独特的微域,
神经元(2)我们将研究胶质细胞FIG-1/血小板反应蛋白在AFD受体吞噬中的作用。
终末和AFD神经元形状。(3)我们将研究磷脂酰丝氨酸受体PSR-1在
AFD结束和形状的吞没。
项目成果
期刊论文数量(0)
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Shai Shaham其他文献
Shai Shaham的其他文献
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{{ truncateString('Shai Shaham', 18)}}的其他基金
Glial control of neuron development and function
神经胶质细胞对神经元发育和功能的控制
- 批准号:
10063060 - 财政年份:2018
- 资助金额:
$ 37.08万 - 项目类别:
Glial control of neuron development and function
神经胶质细胞对神经元发育和功能的控制
- 批准号:
10312039 - 财政年份:2018
- 资助金额:
$ 37.08万 - 项目类别:
Glial Control of Neuron Development and Function
神经胶质对神经元发育和功能的控制
- 批准号:
10528452 - 财政年份:2018
- 资助金额:
$ 37.08万 - 项目类别:
Glial Control of Neuron Development and Function - Administrative Supplement
神经胶质对神经元发育和功能的控制 - 行政补充
- 批准号:
10632281 - 财政年份:2018
- 资助金额:
$ 37.08万 - 项目类别:
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