Serway Christine N, Dunkelberger Brian S, Del Padre Denise, Nolan Nicole W C, Georges Stephanie, Freer Stephanie, Andres Andrew J, de Belle J Steven
School of Life Sciences, University of Nevada, Las Vegas, NV, USA.
Comprehensive Cancer Center, University of New Mexico, Albuquerque, NM, USA.
J Neurogenet. 2020 Mar;34(1):69-82. doi: 10.1080/01677063.2019.1709184. Epub 2020 Jan 22.
Neuronal development and memory consolidation are conserved processes that rely on nuclear-cytoplasmic transport of signaling molecules to regulate gene activity and initiate cascades of downstream cellular events. Surprisingly, few reports address and validate this widely accepted perspective. Here we show that Importin-α2 (Imp-α2), a soluble nuclear transporter that shuttles cargoes between the cytoplasm and nucleus, is vital for brain development, learning and persistent memory in . Mutations in (, known as or and homologous with human ) are alleles of (), a gene known to regulate aspects of brain development and influence adult behavior in flies. Mushroom bodies (MBs), paired associative centers in the brain, are smaller than normal due to defective proliferation of specific intrinsic Kenyon cell (KC) neurons in mutants. Extant KCs projecting to the MB β-lobe terminate abnormally on the contralateral side of the brain. adults have impaired olfactory learning but normal memory decay in most respects, except that protein synthesis-dependent long-term memory (LTM) is abolished. This observation supports an alternative mechanism of persistent memory in which mutually exclusive protein-synthesis-dependent and -independent forms rely on opposing cellular mechanisms or circuits. We propose a testable model of Imp-α2 and nuclear transport roles in brain development and conditioned behavior. Based on our molecular characterization, we suggest that is hereafter referred to as .
神经元发育和记忆巩固是保守的过程，依赖于信号分子的核质运输来调节基因活性并启动下游细胞事件的级联反应。令人惊讶的是，很少有报告探讨和验证这一被广泛接受的观点。在这里，我们表明，输入蛋白-α2（Imp-α2）是一种可溶性核转运蛋白，在细胞质和细胞核之间穿梭运输货物，对大脑发育、学习和持续性记忆至关重要。[此处缺失具体基因名称，原文可能有误]（在果蝇中称为[具体名称]或[具体名称]，与人类[相关基因名称]同源）的突变是[相关基因名称]（[相关基因名称]）的等位基因，该基因已知可调节大脑发育的各个方面并影响果蝇的成年行为。蘑菇体（MBs）是大脑中的成对联想中心，由于[具体基因名称]突变体中特定内在肯扬细胞（KC）神经元的增殖缺陷，其体积比正常情况小。投射到MBβ叶的现存KC在大脑的对侧异常终止。[具体基因名称]成虫的嗅觉学习受损，但在大多数方面记忆衰退正常，只是依赖蛋白质合成的长期记忆（LTM）被消除。这一观察结果支持了一种持续性记忆的替代机制，即相互排斥的依赖蛋白质合成和不依赖蛋白质合成的形式依赖于相反的细胞机制或回路。我们提出了一个关于Imp-α2和核运输在大脑发育和条件行为中的作用的可测试模型。基于我们的分子特征，我们建议将[具体基因名称]此后称为[新名称]。
