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.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 果蝇幼虫神经肌肉接头 (NMJ) 的突触生长和功能需要由肌肉来源的骨形态发生蛋白 (BMP) 和神经元 BMP 受体介导的逆行信号传导。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 型受体一厢情愿 (Wit) 定位于 NMJ 突触纽扣、轴突和运动神经元细胞体的点状结构中。两种受体在运动神经元轴突中顺行和逆行运输；受体运输的受损与通过该途径的信号传导的减少相关。除了彼此独立的 I 型和 II 型受体的顺行和逆行交通之外，我们还检测了 Tkv 和 Wit 的逆行共定位囊泡交通。 Wit 和 Tkv 的这种共定位逆行交通在 gbb 突变体中被破坏，其中信号通路不活跃，并且 II 型受体 Wit 下调。我们提出，共定位受体交通构成了 BMP 信号内体中激活受体的复合体，并且与神经营养素类似，这种 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基因转录突触生长所需的。 LSF 进行的实验的目标是通过基于 FLIM 的 FRET 检测内体中 Wit 和 Tkv 的相互作用。