Gao Andy Y L, Lourdin-De Filippis Etienne, Orlowski John, McKinney R Anne
Integrated Program in Neuroscience, McGill University, Montreal, QC, Canada.
Department of Pharmacology & Therapeutics, McGill University, Montreal, QC, Canada.
Front Physiol. 2022 Apr 25;13:892196. doi: 10.3389/fphys.2022.892196. eCollection 2022.
Endomembrane alkali cation (Na, K)/proton (H) exchangers (eNHEs) are increasingly associated with neurological disorders. These eNHEs play integral roles in regulating the luminal pH, processing, and trafficking of cargo along the secretory (Golgi and post-Golgi vesicles) and endocytic (early, recycling, and late endosomes) pathways, essential regulatory processes vital for neuronal development and plasticity. Given the complex morphology and compartmentalization of multipolar neurons, the contribution of eNHEs in maintaining optimal pH homeostasis and cargo trafficking is especially significant during periods of structural and functional development and remodeling. While the importance of eNHEs has been demonstrated in a variety of non-neuronal cell types, their involvement in neuronal function is less well understood. In this review, we will discuss their emerging roles in excitatory synaptic function, particularly as it pertains to cellular learning and remodeling. We will also explore their connections to neurodevelopmental conditions, including intellectual disability, autism, and attention deficit hyperactivity disorders.
内膜碱金属阳离子（Na、K）/质子（H）交换体（eNHEs）与神经疾病的关联日益密切。这些eNHEs在调节管腔pH值、货物加工以及沿分泌途径（高尔基体和高尔基体后囊泡）和内吞途径（早期、循环和晚期内体）的运输过程中发挥着不可或缺的作用，而这些过程是神经元发育和可塑性所必需的重要调节过程。鉴于多极神经元复杂的形态和区室化结构，在结构和功能发育及重塑阶段，eNHEs在维持最佳pH值稳态和货物运输方面的作用尤为显著。虽然eNHEs在多种非神经元细胞类型中的重要性已得到证实，但其在神经元功能中的作用尚不太清楚。在这篇综述中，我们将讨论它们在兴奋性突触功能中新兴的作用，特别是与细胞学习和重塑相关的作用。我们还将探讨它们与神经发育病症的联系，包括智力残疾、自闭症和注意力缺陷多动障碍。
