ZBP1-mediated transport and local translation of B-actin mRNA in growth cones

ZBP1 介导的生长锥中 B 肌动蛋白 mRNA 的运输和局部翻译

• 批准号: 8011057
• 负责人: Kristy Welshhans
• 金额: $ 2.41万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-01-01 至 2011-05-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8011057
• 关键词: 3' Untranslated Regions; Actins; Affect; Antisense Oligonucleotides; Axon; Binding; Binding Proteins; Cell physiology; Cells; Complex; Cues; Cytoplasmic Granules; Development; Disease; Dissociation; Genetic Translation; Goals; Growth Cones; Knockout Mice; Knowledge; Lentivirus Vector; Life; Location; Mediating; Messenger RNA; Methods; Movement; Nervous system structure; Neurons; Process; Protein Biosynthesis; Proteins; Regulation; Reporter; Research Proposals; Ribonucleoproteins; Role; Structural Protein; Structure; Synapses; System; Testing; Time; Transcript; Translating; Translations; Tubulin; cell motility; innovation; mouse model; mutant; nervous system development; nervous system disorder; neurite growth; prevent; protein complex; research study; response; small hairpin RNA

DESCRIPTION (provided by applicant): The proper development of the nervous system is dependent on a number of cellular processes occurring at the appropriate time and location. One such cellular process that is required for proper nervous system development is the appropriate localization and translation of certain mRNA transcripts. The localization of these transcripts is dependent on mRNA binding proteins, a class of molecules responsible for the transport, and in some cases, translation of their mRNA cargo. Zipcode binding protein 1 (ZBP1) is an mRNA binding protein that is responsible for the transport and regulates the translation of ¿-actin mRNA. ¿-actin is important for the development of the nervous system because it is one of the major structural proteins that composes the growth cone, the pathfinding structure of a developing neuron. The aim of the current proposal is to determine how the loss of ZBP1 affects nervous system development and specifically, the growth cone. It is of great importance to study the function of ZBP1 because it is essential for appropriate gross development. The current proposal has two main goals: 1) to examine the role of ZBP1 in the regulation of axon outgrowth and guidance and 2) to examine the role of ZBP1 in the transport and translation of ¿-actin mRNA. To determine the role of ZBP1 in these processes, lentiviral vector-mediated shRNA interference to ZBP1 will be employed, as well as a ZBP1 knockout mouse model. This proposal also uses innovative fluorescent proteins and reporters in primary neuronal cultures in order to achieve the above stated aims. It is essential to study the localization and translation of ¿-actin mRNA because it encodes a structural protein that is required for proper growth cone motility and guidance, and therefore is required for the correct connectivity of the nervous system to be established. The long-term objective of this proposal is to gain an understanding of the basic mechanisms that are required for axon outgrowth and growth cone guidance, such as local translation of mRNA transcripts within the growth cone; this information will further our knowledge about the appropriate development of the nervous system as a whole. The development of the nervous system is a process during which neurons must find their way to and make connections with their appropriate targets. If this does not happen properly, a number of disease states may result. This proposal investigates the role of the protein ZBP1, which is responsible for transporting mRNA during development; the loss of this protein may result in inappropriate development of the nervous system and thus, a neurological disease state.

描述（由申请人提供）：神经系统的正确发育取决于在适当的时间和地点发生的许多细胞过程，神经系统适当的发育所需的细胞过程之一是某些细胞的适当定位和翻译。这些转录物的定位依赖于 mRNA 结合蛋白，这是一类负责其 mRNA 货物运输和翻译的分子，Zipcode 结合蛋白 1 (ZBP1) 是一种负责 mRNA 结合蛋白。用于运输并规范 ¿ 的翻译-肌动蛋白mRNA。 -肌动蛋白对于神经系统的发育很重要，因为它是构成生长锥的主要结构蛋白之一，生长锥是发育中的神经元的寻路结构。当前提案的目的是确定 ZBP1 的丢失如何影响神经系统。研究 ZBP1 的功能非常重要，因为它对于适当的总体发育至关重要：1）检查 ZBP1 在轴突调节中的作用。生长和指导，2) 检查 ZBP1 在 ¿ 的运输和翻译中的作用为了确定 ZBP1 在这些过程中的作用，将采用慢病毒载体介导的 shRNA 干扰 ZBP1，以及 ZBP1 敲除小鼠模型，该提案还使用了原代神经元培养物中的创新荧光蛋白和生产者。为了实现上述目标，有必要研究¿的本地化和翻译。 -肌动蛋白 mRNA，因为它编码适当生长锥运动和引导所需的结构蛋白，因此是建立神经系统正确连接所必需的。该提案的长期目标是了解轴突生长和生长锥引导所需的基本机制，例如生长锥内 mRNA 转录本的局部翻译；这些信息将进一步了解神经系统作为一个整体的适当发育过程。必须如果这不能正确发生，可能会导致许多疾病状态，该提案研究了蛋白质 ZBP1 的作用，该蛋白质负责在发育过程中运输 mRNA。蛋白质可能导致神经系统发育不当，从而导致神经系统疾病状态。

项目成果

Sonic Hedgehog Guides Axons via Zipcode Binding Protein 1-Mediated Local Translation.

Sonic Hedgehog 通过邮政编码结合蛋白 1 介导的局部翻译来引导轴突。

• 发表时间: 2017
• 作者: Lepelletier, Léa;Langlois, Sébastien D;Kent, Christopher B;Welshhans, Kristy;Morin, Steves;Bassell, Gary J;Yam, Patricia T;Charron, Frédéric
• 通讯作者: Charron, Frédéric

RACK1 is a ribosome scaffold protein for β-actin mRNA/ZBP1 complex.

RACK1 是β-肌动蛋白mRNA/ZBP1 复合物的核糖体支架蛋白。

• 发表时间: 2012
• 影响因子: 3.7
• 作者: Ceci, Marcello;Welshhans, Kristy;Ciotti, Maria Teresa;Brandi, Rossella;Parisi, Chiara;Paoletti, Francesca;Pistillo, Luana;Bassell, Gary J;Cattaneo, Antonino
• 通讯作者: Cattaneo, Antonino