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Spatial organization of actin polymerizaton during axon guidance.

轴突引导期间肌动蛋白聚合的空间组织。

基本信息

批准号：
8534313
负责人：
CHRISTOPHER C QUINN
金额：
$ 7.13万
依托单位：
UNIVERSITY OF WISCONSIN MILWAUKEE
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-09-01 至 2015-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8534313
关键词：
ABI1 gene Actins Address Axon Breast Cancer Cell Caenorhabditis elegans Cancer Patient Cell physiology Cells Complex Cues Cytoskeletal Filaments Cytoskeleton Data Data Reporting Dendrites Development Developmental Biology Diagnosis Event Failure Future Gene Expression Profile Genomics Goals Growth Growth Cones Homologous Gene Investigation Knowledge Lead Link Malignant Neoplasms Mediating Medicine Mental disorders Nervous system structure Neurons Outcome Study Patients Principal Investigator Process Proteins Publishing RNA Interference Recruitment Activity Regulation Research Role Side Signal Transduction Source Staging System Work abstracting axon growth axon guidance base cancer cell cell motility developmental disease extracellular genetic regulatory protein in vivo insight migration nervous system disorder neuronal growth polymerization presynaptic receptor response

项目摘要

DESCRIPTION (provided by applicant): Many of the intracellular components that allow neuronal growth cones to interpret and respond to extracellular guidance cues have been identified, but we lack an understanding of how these components function to establish asymmetry in the growth cone. C. elegans provides an excellent system to address this question, because it is possible to observe the localization of proteins within a neuron as it responds to a guidance cue in vivo. In the HSN neuron of C. elegans, UNC-40 (also known as DCC) receptor becomes asymmetrically localized to the side of the cell closest to the source of the UNC-6 (also known as netrin) guidance cue. This in turn, leads to asymmetric recruitment of MIG-10 (also known as lamellipodin), which has an outgrowth-promoting activity, thereby causing outgrowth towards the source of UNC-6 guidance cue. The outgrowth-promoting activity of MIG-10 is thought to result from actin polymerization, but the link between MIG-10 and the actin cytoskeleton is not understood. The objective of this proposal is to determine how MIG-10 links to the actin cytoskeleton to cause a directional outgrowth-promoting activity. Our hypothesis is that MIG-10 (lamellipodin) promotes directional outgrowth by asymmetrically recruiting the WAVE actin regulatory complex. It is expected that the results from these studies will allow us to build an understanding of how signaling complexes can spatially organize actin regulatory proteins to promote growth in response to axon guidance cues. Furthermore, it is likely that the results of these studies will have broader significance because UNC-40 and MIG-10 have been implicated in a wide variety of other morphogenetic events and emerging evidence suggests that asymmetric localization is a key part of their roles in these processes.

描述（由申请人提供）：许多允许神经元生长锥解释和响应细胞外引导信号的细胞内成分已被识别，但我们对这些成分如何发挥作用以在生长锥中建立不对称性缺乏了解。线虫提供了一个很好的系统来解决这个问题，因为当神经元响应体内的引导信号时，可以观察到蛋白质在神经元内的定位。在秀丽隐杆线虫的 HSN 神经元中，UNC-40（也称为 DCC）受体不对称地定位于最靠近 UNC-6（也称为 netrin）引导信号源的细胞一侧。这反过来又导致 MIG-10（也称为板脂蛋白）的不对称募集，其具有促进生长的活性，从而导致向 UNC-6 引导信号源的生长。 MIG-10 的生长促进活性被认为是肌动蛋白聚合的结果，但 MIG-10 与肌动蛋白细胞骨架之间的联系尚不清楚。该提案的目的是确定 MIG-10 如何与肌动蛋白细胞骨架连接以引起定向生长促进活性。我们的假设是 MIG-10（片状蛋白）通过不对称招募 WAVE 肌动蛋白调节复合物来促进定向生长。预计这些研究的结果将使我们能够了解信号复合物如何在空间上组织肌动蛋白调节蛋白以响应轴突引导线索促进生长。此外，这些研究的结果可能具有更广泛的意义，因为 UNC-40 和 MIG-10 与多种其他形态发生事件有关，并且新出现的证据表明，不对称定位是它们在这些过程中发挥作用的关键部分。