CHARACTERIZATION OF AXONAL TRANSPORT OF A BMP SIGNALING ENDOSOME

BMP 信号内体轴突运输的表征

• 批准号: 7956528
• 负责人: GUILLERMO MARQUES
• 金额: $ 1.32万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-01 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7956528
• 关键词: Axon; Axonal Transport; Bone Morphogenetic Proteins; Cell Nucleus; Complex; Computer Retrieval of Information on Scientific Projects Database; Drosophila genus; Endosomes; Fluorescence; Fluorescence Resonance Energy Transfer; Funding; Genetic Transcription; Goals; Grant; Growth; Impairment; Institution; Laboratories; Larva; Mediating; Motor Neurons; Muscle; Neuromuscular Junction; Neurons; Pathway interactions; Presynaptic Terminals; Research; Research Personnel; Resources; Signal Pathway; Signal Transduction; Source; Structure; Synapses; Thick; Thinking; United States National Institutes of Health; Veins; Wit; base; bone morphogenetic protein receptors; mutant; neuronal cell body; neurotrophic factor; receptor; research study; trafficking

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Synaptic growth and function of the Drosophila larva neuromuscular junction (NMJ) requires retrograde signaling mediated by muscle-derived Bone Morphogenetic Proteins (BMPs) and neuronal BMP receptors. How signaling at the synaptic terminal is relayed to the cell body and nucleus to regulate transcription is unknown. We find that the type I receptor Thick veins (Tkv) and the type II receptor Wishful thinking (Wit) localize in punctate structures at the NMJ synaptic boutons, axons, and cell body of motoneurons. Both receptors traffic anterogradely and retrogradely in motoneurons axons; and impairment of receptor traffic correlates with a decrease in signaling through the pathway. In addition to anterograde and retrograde traffic of type I and type II receptors independently of each other, we also detect retrograde co-localized vesicular traffic of Tkv and Wit. This co-localized retrograde traffic of Wit and Tkv is disrupted in gbb mutants where the signaling pathway is inactive, and the type II receptor Wit is down regulated. We propose that co-localized receptor traffic constitutes a complex of the activated receptors in a BMP signaling endosome and that similar to neurotrophins, this BMP signaling endosome relays the Gbb signal from the synaptic terminal to the cell body to activate downstream effectors and transcription of genes required for synaptic growth. The goal of the experiments to be performed at LSF is to detect the interaction of Wit and Tkv in endosomes by FLIM-based FRET.

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 果蝇幼虫神经肌肉接头(NMJ)的突触生长和功能需要肌源性骨形态发生蛋白(BMPs)和神经元性BMP受体介导的逆行信号。突触末端的信号如何传递到细胞体和细胞核以调节转录尚不清楚。我们发现，I型受体粗静脉(Tkv)和II型受体如意思维(Wit)定位于NMJ突触突触、轴突和运动神经元细胞体的点状结构中。这两种受体在运动神经元轴突中的顺行和逆行交通；受体交通的损害与通过该通路的信号减少有关。除了I型和II型受体相互独立的顺行和逆行交通外，我们还检测到Tkv和Wit的逆行共同定位的囊泡交通。这种共同定位的Wit和Tkv的逆行交通在GBB突变体中被扰乱，其中信号通路不活跃，II型受体Wit下调。我们认为，共定位的受体交通构成了BMP信号内体中激活的受体的复合体，类似于神经营养因子，BMP信号内体将GBB信号从突触末端传递到细胞体，以激活下游效应器和突触生长所需基因的转录。在LSF进行的实验的目标是通过基于FLIM的FRET来检测内体中Wit和Tkv的相互作用。