Gyurkó M Dávid, Csermely Péter, Sőti Csaba, Steták Attila
Semmelweis University, Department of Medical Chemistry, Budapest, Üllői út 26 1085, Hungary.
University of Basel, Transfaculty Research Platform Molecular and Cognitive Neurosciences, Birmannsgasse 8, 4055 Basel, Switzerland.
Sci Rep. 2015 Oct 15;5:15084. doi: 10.1038/srep15084.
The Ras GTPase activating proteins (RasGAPs) are regulators of the conserved Ras/MAPK pathway. Various roles of some of the RasGAPs in learning and memory have been reported in different model systems, yet, there is no comprehensive study to characterize all gap genes in any organism. Here, using reverse genetics and neurobehavioural tests, we studied the role of all known genes of the rasgap family in C. elegans in associative learning and memory. We demonstrated that their proteins are implicated in different parts of the learning and memory processes. We show that gap-1 contribute redundantly with gap-3 to the chemosensation of volatile compounds, gap-1 plays a major role in associative learning, while gap-2 and gap-3 are predominantly required for short- and long-term associative memory. Our results also suggest that the C. elegans Ras orthologue let-60 is involved in multiple processes during learning and memory. Thus, we show that the different classes of RasGAP proteins are all involved in cognitive function and their complex interplay ensures the proper formation and storage of novel information in C. elegans.
Ras GTP酶激活蛋白（RasGAPs）是保守的Ras/丝裂原活化蛋白激酶（MAPK）信号通路的调节因子。在不同的模型系统中，已报道了一些RasGAPs在学习和记忆中的多种作用，然而，尚无全面研究来表征任何生物体中的所有GAP基因。在此，我们利用反向遗传学和神经行为测试，研究了秀丽隐杆线虫中rasgap家族所有已知基因在联想学习和记忆中的作用。我们证明它们的蛋白质参与了学习和记忆过程的不同部分。我们发现，gap-1与gap-3在挥发性化合物的化学感受方面发挥冗余作用，gap-1在联想学习中起主要作用，而gap-2和gap-3主要参与短期和长期联想记忆。我们的结果还表明，秀丽隐杆线虫的Ras同源物let-60参与学习和记忆过程中的多个环节。因此，我们表明不同类别的RasGAP蛋白均参与认知功能，它们之间复杂的相互作用确保了秀丽隐杆线虫中新型信息的正确形成和存储。
