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一种名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释放出来，并在一个称为突触神经传递的过程中与存在于相邻细胞膜上的受体蛋白结合。氨基酸类神经递质谷氨酸及其结合的谷氨酸受体负责哺乳动物大脑中的大部分兴奋性神经传递。谷氨酸受体是由四个亚基组成的蛋白质复合体，它们以不同的组合组合在一起，产生不同类型和性质的膜嵌入离子通道。近年来，谷氨酸受体受到多种辅助因子的作用，这些辅助因子调节突触的通道特性和定位。因此，阐明谷氨酸受体的一般结构和功能，以及这些受体是如何通过与辅助蛋白的关联来调节的，对于理解大脑生理学的基本原理是至关重要的。这笔赠款将集中在AMPA型谷氨酸受体与SynDIG蛋白家族的相互作用上。我们将结合分子生物学、生物化学和电生理学实验来验证这一假说，即SynDIG蛋白影响AMPA型谷氨酸受体向突触后膜细胞表面的传递，并改变对突触神经传递至关重要的谷氨酸受体通道的离子流动特性。拟议研究的更广泛影响包括整合国际科学研究所的研究和教育活动，特别是在扩大来自代表性不足群体(主要是西班牙裔/拉丁裔)攻读科学研究生学位的本科生参与的背景下。本科生的参与将由PI与实验室的研究生一起指导，从而整合研究、教学和科学界为在实验室攻读研究生的学生而开展的外展活动。此外，本科生和研究生将参加国际交流，作为与以色列和平协会合作开展这一项目的一部分，该项目由国家科学基金会和美国-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.