Abstract:
The N-methyl-D-aspartate (NMDA) glutamate receptors function as plasma membrane ionic channels and take part in very tightly controlled cellular processes activating neurogenic and inflammatory pathways. In particular, the NR1 subunit (new terminology: GluN1) is required for many neuronal and non-neuronal cell functions, including plasticity, survival, and differentiation. Physiologic levels of glutamate agonists and NMDA receptor activation are required for normal neuronal functions such as neuronal development, learning, and memory. When glutamate receptor agonists are present in excess, binding to NMDA receptors produces neuronal/CNS/PNS long-term potentiation, conditions of acute pain, ongoing severe intractable pain, and potential excitotoxicity and pathology. The GluNR1 subunit (116 kD) is necessary as the anchor component directing ion channel heterodimer formation, cellular trafficking, and the nuclear localization that directs functionally specific heterodimer formation, cellular trafficking, and nuclear functions. Emerging studies report the relevance of GluN1 subunit composition and specifically that nuclear GluN1 has major physiologic potential in tissue and/or subnuclear functioning assignments. The shift of the GluN1 subunit from a surface cell membrane to nuclear localization assigns the GluN1 promoter immediate early gene behavior with access to nuclear and potentially nucleolar functions. The present narrative review addresses the nuclear translocation of GluN1, focusing particularly on examples of the role of GluN1 in nociceptive processes.
摘要:
N-甲基-D-天冬氨酸(NMDA)谷氨酸受体起质膜离子通道的作用,并参与非常严格控制的细胞过程,激活神经源性和炎症途径。特别是,NR1亚基(新术语:GluN1)是许多神经元和非神经元细胞功能所必需的,包括可塑性,生存,和差异化。谷氨酸激动剂和NMDA受体激活的生理水平是正常神经元功能所必需的,如神经元发育,学习,和记忆。当谷氨酸受体激动剂过量存在时,与NMDA受体结合产生神经元/CNS/PNS长时程增强,急性疼痛的条件,持续严重的顽固性疼痛,以及潜在的兴奋性毒性和病理学。GluNR1亚基(116kD)作为指导离子通道异二聚体形成的锚定成分是必需的,细胞贩运,以及指导功能特异性异二聚体形成的核定位,细胞贩运,核功能。新兴研究报告了GluN1亚基组成的相关性,特别是核GluN1在组织和/或核下功能分配中具有主要的生理潜力。GluN1亚基从表面细胞膜转移到核定位使GluN1启动子立即具有早期基因行为,可以获得核功能和潜在的核仁功能。本叙述性综述涉及GluN1的核易位,特别着重于GluN1在伤害性过程中的作用的例子。