ICOB: Investigation of AMPA-type glutamate receptor interaction with the accessory SynDIG protein family

神经系统中的细胞间通讯是由称为神经递质的小化学物质介导的，这些化学物质从一个细胞中释放出来，并在一个称为突触神经传递的过程中与相邻细胞膜上的受体蛋白结合。氨基酸神经递质谷氨酸及其共轭谷氨酸受体负责哺乳动物脑中的大多数兴奋性神经传递。谷氨酸受体是四个亚基的蛋白质复合物，它们以各种组合组装，产生不同类型和性质的膜嵌入离子通道。近年来，越来越多的证据表明，谷氨酸受体受各种辅助因子的作用，这些辅助因子调节通道特性和突触定位。因此，阐明一般谷氨酸受体的结构和功能，以及这些受体如何通过与辅助蛋白的结合来调节，对于理解脑生理学的基本原理至关重要。这项资助将集中在AMPA型谷氨酸受体与SynDIG蛋白家族的相互作用上。将进行分子生物学、生物化学和电生理学实验的组合以检验SynDIG蛋白影响AMPA型谷氨酸受体向突触后膜的细胞表面的递送以及改变离子流通过对突触神经传递至关重要的谷氨酸受体通道的性质的假设。拟议研究的更广泛影响包括PI的研究和教育活动的整合，特别是在扩大来自代表性不足的群体（主要是西班牙裔/拉丁裔）的本科生参与的背景下，追求科学研究生学位。本科生的参与将由PI与实验室的研究生一起指导，从而为在实验室攻读研究生的学生整合研究，教学和科学界的外联活动。此外，本科生和研究生将参加国际交流，作为与以色列PI合作的一部分，该项目由NSF和美国-以色列两国科学基金会共同支持。

Cell-to-cell communication in the nervous system is mediated by small chemicals called neurotransmitters that are released from one cell and bind to receptor proteins present on the membrane of the adjacent cell in a process called synaptic neurotransmission. The amino-acid neurotransmitter glutamate and its conjugate glutamate receptors are responsible for the majority of the excitatory neurotransmission in the mammalian brain. Glutamate receptors are protein complexes of four subunits that assemble in various combinations, creating membrane-embedded ion-channels of different types and properties. In recent years, it has become increasingly evident that glutamate receptors are acted on by various auxiliary factors that regulate channel properties and localization at synapses. Therefore, elucidating the structure and function of glutamate receptors in general, and how these receptors are modulated by association with accessory proteins in particular, is central to understanding the basic principles of brain physiology. This grant will concentrate on the interaction of the AMPA-type glutamate receptors with the SynDIG protein family. A combination of molecular biology, biochemistry and electrophysiology experiments will be undertaken to test the hypothesis that SynDIG proteins influence the delivery of AMPA-type glutamate receptors to the cell surface of the postsynaptic membrane as well as alter the properties of ion flow through the glutamate receptor channel critical for synaptic neurotransmission. The broader impacts of the proposed studies include integration of the research and education activities of the PI, specifically in the context of broadening the participation of undergraduate students from underrepresented groups (primarily Hispanic/Latino) pursuing postgraduate degrees in science. Undergraduate participation will be directed by the PI in conjunction with graduate students in the laboratory, thereby integrating research, teaching, and scientific community outreach activities for students pursuing graduate studies in the laboratory. Additionally undergraduate and graduate students will participate in international exchanges as part of the collaboration with the Israeli PI for this project which is jointly supported by NSF and United States-Israel Binational Science Foundation.