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.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 果蝇幼虫神经肌肉结（NMJ）的突触生长和功能需要由肌肉衍生的骨形态发生蛋白（BMP）和神经元BMP受体介导的逆行信号传导。突触末端的信号传导如何传递到细胞体和细胞核以调节转录。我们发现，I型受体厚静脉（TKV）和II型受体一厢情愿（机智）位于NMJ突触式胸子，轴突和运动神经元的细胞体的点状结构中。两种受体在运动神经元轴突中逆转和逆行。受体流量的损害与通过途径的信号传导减少相关。除了彼此独立于I型和II型受体的顺行和逆行流量外，我们还检测到TKV和WIT的逆行共定位的囊泡流量。在信号通路不活动的GBB突变体中，这种WIT和TKV的共定位逆行流量被破坏，并且II型受体机智被调节。我们提出，共定位的受体流量构成了BMP信号内体中活化受体的复合物，并且与神经营养蛋白相似，该BMP信号内体内体传递了GBB信号从突触端终端转移到细胞体，以激活下游的下游效应和突发性生长所需的基因转录。 在LSF上进行的实验的目的是通过基于FLIM的FRET检测WIT和TKV在内体中的相互作用。