RIG/CAA: A Novel Family of Transmembrane Proteins that Regulate Synaptic Differentiation

人类大脑由大约1000亿个神经元组成，这些神经元通过被称为突触的特定细胞之间的接触精确地组织成网络，突触产生诸如情感、学习和记忆以及感知等认知现象。在发育过程中，神经元突触形成了复杂而精确的模式。突触的形成是由突触前和突触后细胞表面的特殊蛋白质在细胞-细胞接触时启动的。Elva Diaz博士（首席研究员）和她的实验室成员已经在突触后神经元细胞表面发现了一组新的相关蛋白质。有趣的是，这个新基因家族的不同家族成员在特定的大脑区域表达，这表明这些分子在决定突触特异性方面发挥着作用。他们的假设是，这些蛋白质参与突触后分化，并向突触前神经元传递信号，导致突触囊泡的募集，这是形成新突触的第一步。在这个应用程序中，Diaz博士提出了在小鼠中使用遗传操作和方法来识别与这些蛋白质相互作用的其他分子的实验，以了解这类有趣的蛋白质在突触形成过程中如何起作用。拟议活动的更广泛影响包括整合研究和教育活动，特别是在扩大代表性不足群体（主要是西班牙裔/拉丁裔）的本科生参与的背景下。作为校园项目的积极参与者，旨在增加未被充分代表的学生攻读科学研究生学位的数量，Diaz博士在招募这些学生到她的实验室作为该提案的研究团队成员方面处于有利地位。本科生的参与将由Diaz博士与实验室的博士生一起指导，从而为在Diaz实验室攻读研究生课程的学生整合研究、教学和社区外展活动。

The human brain comprises ~100 billion neurons precisely organized into networks by specific cell-cell contacts called synapses that give rise to cognitive phenomena such as emotion, learning and memory, and perception. During development, the intricate and precise patterns of neuronal synapses are formed. Synapse formation is initiated by special proteins at the presynaptic and postsynaptic cell surfaces upon cell-cell contact. Dr. Elva Diaz (Principal Investigator) and members of her laboratory have identified a new group of related proteins that are found at the postsynaptic neuronal cell surface. Interestingly, different family members of this new gene family are expressed in specific brain regions, suggesting a role for these molecules in determining synaptic specificity. Their hypothesis is that these proteins are involved in postsynaptic differentiation and transmit signals to the presynaptic neuron to cause recruitment of synaptic vesicles, the first step in the formation of new synapses. In this application, Dr. Diaz proposes experiments using genetic manipulations in mice and methods to identify other molecules with which these proteins interact in order to understand how this interesting class of proteins functions during synapse formation.The broader impacts of the proposed activities include integration of the research and education activities specifically in the context of broadening the participation of undergraduate students from underrepresented groups (primarily Hispanic/Latino). As an active participant in campus programs aimed to increase the number of underrepresented students pursuing postgraduate degrees in science, Dr. Diaz is in a strong position to recruit such students to her laboratory as members of the research team for this proposal. Undergraduate participation will be directed by Dr. Diaz in conjunction with doctoral students in the laboratory, thereby integrating research, teaching, and community outreach activities for students pursuing graduate studies in the Diaz laboratory.