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Molecular Mechanisms Of Synaptic Transmission

突触传递的分子机制

基本信息

批准号：
8565491
负责人：
David Robinson
金额：
$ 38.42万
依托单位：
NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/8565491
关键词：
AMPA Receptors Adhesions Annual Reports Antibodies Axon Binding Binding Proteins Biochemistry Biological Assay Biology Cell Adhesion Molecules Cell Culture Techniques Cell Line Cell Proliferation Cellular biology China Cochlea Collaborations Communication Dendrites Development Diagnosis Disease Ectopic Expression Electron Microscope Equipment Excitatory Synapse Fluorescence Recovery After Photobleaching Gifts Glutamate Receptor Hair Cells Hippocampus (Brain)Histology Image In Vitro International Investigation Journals Knockout Mice Laboratories Lasers Lead Location MAPK3 gene Maintenance Manuscripts Metabotropic Glutamate Receptors Methods Microscope Microscopy Molecular Molecular Biology Techniques N-Methylaspartate National Institute of Neurological Disorders and Stroke National Institute on Deafness and Other Communication Disorders Neuraxis Neurons Neuropharmacology Neurosciences Paper Phase Preparation Process Protein Tyrosine Kinase Proteins Published Comment Publishing Regulation Reporting Research Research Personnel Resolution Role Scaffolding Protein Science Signal Pathway Supporting Cell Synapses Synaptic Transmission System Tail Transgenic Mice Vertebral column Visual Work follow-up frontier interest kainate melanocyte melanoma member nervous system disorder neuropathology plasmid DNA receptor receptor binding research study scaffold synaptic function trafficking transmission process tumorigenesis vector

项目摘要

The lab has continued to do some neuron cell culture preparations as needed by these researchers. We also oversee maintenance of the JEOL 1010 transmission electron microscope and related equipment, as well as the Zeiss LSM710 laser confocal microscope and Leica Biowave System, which continued to be used here by some of these researchers, and others from adjacent NIDCD labs, in FY12. Ronald Petralia and Ya-Xian Wang continued on several projects begun in FY11 and which were described in last years annual report, and began some new ones in FY12. These are described in detail in the annual report of the new Advanced Imaging Core. However, we have included the associated published works here also in this report, since most of them were begun in FY11 in this project. Otherwise, we will summarize here specifically the work of Gail Seabold, Kai Chang, and Chan-Ying Zheng. Gail Seabold worked to finish two projects while she was here in FY12. She completed the revisions of her major paper on the synaptic adhesion-like molecule, SALM1, and the role of dileucine and PDZ-binding motifs in its trafficking in hippocampal neurons. This work was a collaboration with Ronald Petralia, Robert Wenthold, and Ya-Xian Wang, along with former members of the laboratory, Philip Wang and Kai Chang. It finally was published in the Journal of Biological Chemistry in early 2012, and was featured for the cover photo of the issue. She also worked with Ronald Petralia (and Martin Horak) on a large review paper on glutamate receptor trafficking and plasticity that was published on-line in the Spring of 2012. Gail also worked with Ronald Petralia on some preliminary new studies that are in progress. In addition, Gail was of great benefit in the laboratory, helping to organize and cull through antibodies, DNA plasmids, and other materials in the laboratory, as well as helping out in the laboratory in general. Kai Chang has used techniques of molecular biology, cell biology and histology, to characterize melanomas from several strains of transgenic mice for the metabotropic glutamate receptor, mGluR5 (Choi K.Y and Chang K., et al. PNAS 108 (37): 15219-15224, 2011). In the next phase of study on mGluR5-induced melanoma, he focused on the molecular mechanisms that lead to tumorigenesis of melanocytes by mGluR5 ectopic expression. His major accomplishments in this include: unraveled the signal pathways of ERK1/2 activation in mGluR5-transfected melanocytes, characterized proteins involved in melanomagenesis induced by mGluR5 (potentially useful in diagnosis and therapy), elucidated the function of different mGluR5 domains and showed that ectodomain shedding was associated with cell proliferation, established a melan-a transforming assay and stable melan-a cell lines expressing mGluRs, useful for in vitro tumorigenesis assays, and studied non-receptor tyrosine kinases that may bind to the C-tail of mGluRs and function as co-receptors. Chan-Ying Zheng had three papers with Ronald Petralia and Ya-Xian Wang during 2011, including 2 research papers published in collaboration with Drs. Wenthold and Kachar. These were follow-up papers to one published by these three in 2010. One was a description of fluorescence recovery after photobleaching of pEGFP vector in spines of cultured hippocampal neurons, published in the Journal of Visual Experiments. Another was a study on super resolution microscopy that revealed the slightly different localization of the MAGUKs (synaptic scaffolding proteins), SAP102 and PSD-95 a difference that required super resolution to identify. The third was a review article on the scaffolding proteins, MAGUKs, and their role in synaptic development and plasticity. This was published in the Neuroscientist, and also was used for the cover photo for that issue. After Chan-Ying joined the laboratory of Dr. Katherine Roche in NINDS, she began studying the trafficking and function of two AMPA receptor binding proteins, Gamma 8 and Cornichon 2. These projects are ongoing. Recently, she received two knockout (KO) mice. The Gamma 2 KO mice were purchased from Jackson Laboratories and Gamma 8 KO mice were gifts from Dr. Roger Nicolls group. Chan-Ying is working on Gamma 8 and Cornichon 2 projects using imaging and biochemistry methods. She recently contributed to a Cornichon 2 paper, which has been submitted by the Nicoll group last month. She is the third author of that paper. Also this year, Chan-Ying has been actively reviewing papers submitted to journals by other research groups. She has reviewed 10 manuscripts since November 2011. Half of them were referred by Ronald Petralia, who helped to review her comments in her reviews. The journals that she reviewed include: 2011-- Journal of Molecular Cell Biology, Science China, Frontiers in Biology. 2012-Plos One*(2 papers), Communicative & Integrative Biology, Neuropharmacology, International Journal of Developmental Neuroscience*(2 papers), Acta Pharmacologica Sinica. Chan-Ying will continue her work with Katherine Roche into FY13.

实验室继续根据这些研究人员的需要做一些神经元细胞培养的准备工作。我们还监督JEOL 1010透射电子显微镜和相关设备的维护，以及蔡司LSM 710激光共聚焦显微镜和徕卡生物波系统，其中一些研究人员继续在这里使用，其他人来自邻近的NIDCD实验室，在2012财年。罗纳德Petralia和Ya-Xian Wang继续进行在FY 11开始的几个项目，这些项目在去年的年度报告中有所描述，并在FY 12开始了一些新的项目。这些都在新的高级成像核心的年度报告中详细描述。然而，我们在本报告中也包括了相关的出版作品，因为其中大部分是在本项目的FY 11开始的。除此之外，我们将在这里特别总结盖尔·西博尔德、张凯和郑灿英的工作。 Gail Seabold在FY 12期间完成了两个项目。她完成了她的主要论文的修订突触粘附样分子，SALM 1，和双亮氨酸和PDZ结合基序在其运输海马神经元的作用。这项工作是与罗纳德佩特拉利亚，罗伯特温特霍尔德，王亚贤，沿着与实验室的前成员，菲利普王和张凯合作。它最终于2012年初发表在《生物化学杂志》上，并成为该杂志的封面照片。她还与罗纳德Petralia（和马丁Horak）在一篇关于谷氨酸受体贩运和可塑性的大型评论论文上合作，该论文于2012年春季在线发表。盖尔还与罗纳德佩特拉利亚合作进行了一些初步的新研究，这些研究正在进行中。此外，盖尔在实验室里也有很大的帮助，帮助组织和挑选抗体、DNA质粒和实验室里的其他材料，以及在实验室里帮忙。 Kai Chang已经使用分子生物学、细胞生物学和组织学技术来表征来自代谢型谷氨酸受体mGluR 5的几种转基因小鼠品系的黑素瘤（Choi K.Y和Chang K.，等人PNAS 108（37）：15219-15224，2011）。在mGluR 5诱导的黑色素瘤的下一阶段研究中，他专注于通过mGluR 5异位表达导致黑色素细胞肿瘤发生的分子机制。他在这方面的主要成就包括：阐明了mGluR 5转染的黑素细胞中ERK 1/2激活的信号通路，表征了参与mGluR 5诱导的黑素瘤发生的蛋白质（可能用于诊断和治疗），阐明了不同mGluR 5结构域的功能，并显示胞外域脱落与细胞增殖相关，建立了可用于体外肿瘤发生测定的melan-a转化测定和表达mGluR的稳定的melan-a细胞系，并研究了可结合mGluR的C-尾并作为共受体起作用的非受体酪氨酸激酶。 2011年，郑灿英与罗纳德·彼得拉利亚和王雅贤合作发表了三篇论文，其中包括与温特霍尔德博士和卡查尔博士合作发表的两篇研究论文。这些是这三人在2010年发表的一篇论文的后续论文。一个是在pEGFP载体在培养的海马神经元的棘中光漂白后荧光恢复的描述，发表在视觉实验杂志上。另一项是对超分辨率显微镜的研究，揭示了MAGUKs（突触支架蛋白），SAP 102和PSD-95的位置略有不同，这需要超分辨率来识别。第三篇是关于支架蛋白MAGUKs及其在突触发育和可塑性中的作用的综述文章。这张照片发表在《神经科学家》上，也被用在了那期的封面照片上。陈莹加入NINDS凯瑟琳罗氏博士的实验室后，她开始研究两种AMPA受体结合蛋白Gamma 8和Cornichon 2的运输和功能。这些项目正在进行中。最近，她收到了两只敲除（KO）小鼠。Gamma 2 KO小鼠购自杰克逊实验室，Gamma 8 KO小鼠是Roger Nicolls博士组赠送的。陈英正在使用成像和生物化学方法进行伽马8和Cornichon 2项目。她最近为一篇Cornichon 2论文做出了贡献，该论文已于上个月由Nicoll小组提交。她是这篇论文的第三作者。也是在这一年，詹英一直在积极审查其他研究小组提交给期刊的论文。自2011年11月以来，她已经审查了10份手稿。其中一半是由罗纳德佩特拉利亚推荐的，她帮助审查了她在评论中的评论。 2011-- Journal of Molecular Cell Biology，Science China，Frontiers in Biology. 2012-Plos One*（2篇），沟通与整合生物学，神经药理学，国际发育神经科学杂志 *（2篇），药理学报。陈英将继续她的工作与凯瑟琳罗氏到2013财年。

项目成果

期刊论文数量（20）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Subcellular localization of Patched and Smoothened, the receptors for Sonic hedgehog signaling, in the hippocampal neuron.

DOI：
10.1002/cne.22681
发表时间：
2011-12-15
期刊：
JOURNAL OF COMPARATIVE NEUROLOGY
影响因子：
2.5
作者：
Petralia, Ronald S.;Schwartz, Catherine M.;Wang, Ya-Xian;Mattson, Mark P.;Yao, Pamela J.
通讯作者：
Yao, Pamela J.

mGRASP enables mapping mammalian synaptic connectivity with light microscopy.

DOI：
10.1038/nmeth.1784
发表时间：
2011-12-04
期刊：
NATURE METHODS
影响因子：
48
作者：
Kim, Jinhyun;Zhao, Ting;Petralia, Ronald S.;Yu, Yang;Peng, Hanchuan;Myers, Eugene;Magee, Jeffrey C.
通讯作者：
Magee, Jeffrey C.

Trafficking of the NMDAR2B receptor subunit distal cytoplasmic tail from endoplasmic reticulum to the synapse.

DOI：
10.1371/journal.pone.0039585
发表时间：
2012
期刊：
PloS one
影响因子：
3.7
作者：
Standley S;Petralia RS;Gravell M;Hamilton R;Wang YX;Schubert M;Wenthold RJ
通讯作者：
Wenthold RJ

Organization of NMDA receptors at extrasynaptic locations.

DOI：
10.1016/j.neuroscience.2010.01.022
发表时间：
2010-04-28
期刊：
NEUROSCIENCE
影响因子：
3.3
作者：
Petralia, R. S.;Wang, Y. X.;Hua, F.;Yi, Z.;Zhou, A.;Ge, L.;Stephenson, F. A.;Wenthold, R. J.
通讯作者：
Wenthold, R. J.

Intranasal immunization of the combined lipooligosaccharide conjugates protects mice from the challenges with three serotypes of Moraxella catarrhalis.