比利时鲁汶大学Pierre Vanderhaeghen等研究人员合作发现，LRRC37B是大脑皮层神经元电压门控钠通道和轴突兴奋性的人类调节因子。这一研究成果发表在2023年12月21日出版的国际学术期刊《细胞》上。
研究人员报告了人类特异性基因LRRC37B编码一种在人类皮层锥体神经元（CPN）中表达的受体，并选择性地定位于轴突起始节段（AIS），即触发动作电位的亚细胞区。LRRC37B在小鼠CPN体内异位表达会导致固有兴奋性降低，这是人类CPN某些类别的显著特征。分子上，LRRC37B与分泌配体FGF13A和电压门控钠通道（Nav）β亚基SCN1B结合。LRRC37B能集中FGF13A对Nav通道功能的抑制作用，从而降低兴奋性，特别是在AIS水平。
成人大脑皮层切片的电生理记录显示，表达LRRC37B的人类CPN神经元兴奋性较低。因此，LRRC37B是人类神经元兴奋性的物种特异性调节因子，将人类基因组和细胞演化联系在一起，对人类大脑功能和疾病具有重要意义。
研究人员表示，人类认知能力的增强源于神经元和神经回路的特化特征。
附：英文原文
Title: LRRC37B is a human modifier of voltage-gated sodium channels and axon excitability in cortical neurons
Author: Baptiste Libé-Philippot, Amélie Lejeune, Keimpe Wierda, Nikolaos Louros, Emir Erkol, Ine Vlaeminck, Sofie Beckers, Vaiva Gaspariunaite, Angéline Bilheu, Katerina Konstantoulea, Hajnalka Nyitrai, Matthias De Vleeschouwer, Kristel M. Vennekens, Niels Vidal, Thomas W. Bird, Daniela C. Soto, Tom Jaspers, Maarten Dewilde, Megan Y. Dennis, Frederic Rousseau, Davide Comoletti, Joost Schymkowitz, Tom Theys, Joris de Wit, Pierre Vanderhaeghen
Issue&Volume: 2023/12/21
Abstract: The enhanced cognitive abilities characterizing the human species result from specialized features of neurons and circuits. Here, we report that the hominid-specific gene LRRC37B encodes a receptor expressed in human cortical pyramidal neurons (CPNs) and selectively localized to the axon initial segment (AIS), the subcellular compartment triggering action potentials. Ectopic expression of LRRC37B in mouse CPNs in vivo leads to reduced intrinsic excitability, a distinctive feature of some classes of human CPNs. Molecularly, LRRC37B binds to the secreted ligand FGF13A and to the voltage-gated sodium channel (Nav) β-subunit SCN1B. LRRC37B concentrates inhibitory effects of FGF13A on Nav channel function, thereby reducing excitability, specifically at the AIS level. Electrophysiological recordings in adult human cortical slices reveal lower neuronal excitability in human CPNs expressing LRRC37B. LRRC37B thus acts as a species-specific modifier of human neuron excitability, linking human genome and cell evolution, with important implications for human brain function and diseases.
DOI: 10.1016/j.cell.2023.11.028
Source: https://www.cell.com/cell/fulltext/S0092-8674(23)01314-4