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哺乳动物中枢神经系统中缝隙连接及其组成成分连接蛋白的结构与功能

Structure and Functions of Gap Junctions and Their Constituent Connexins in the Mammalian CNS.

作者信息

Kirichenko E Yu, Skatchkov S N, Ermakov A M

机构信息

Academy of Biology and Biotechnology, Southern Federal University, Rostov-on-Don, 344090 Russia.

Department of Biochemistry, School of Medicine, P.O. Box 60327, Universidad Central del Caribe, Bayamón, PR, 00960-6032 USA.

出版信息

Biochem (Mosc) Suppl Ser A Membr Cell Biol. 2021 Apr;15(2):107-119. doi: 10.1134/s1990747821020069. Epub 2021 Jun 10.

Abstract

Numerous data obtained in the last 20 years indicate that all parts of the mature central nervous system, from the retina and olfactory bulb to the spinal cord and brain, contain cells connected by gap junctions (GJs). The morphological basis of the GJs is a group of joined membrane hemichannels called connexons, the subunit of each connexon is the protein connexin. In the central nervous system, connexins show specificity and certain types of them are expressed either in neurons or in glial cells. Connexins and GJs of neurons, combining certain types of inhibitory hippocampal and neocortical neuronal ensembles, provide synchronization of local impulse and rhythmic activity, thalamocortical conduction, control of excitatory connections, which reflects their important role in the processes of perception, concentration of attention and consolidation of memory, both on the cellular and at the system level. Connexins of glial cells are ubiquitously expressed in the brain, and the GJs formed by them provide molecular signaling and metabolic cooperation and play a certain role in the processes of neuronal migration during brain development, myelination, tissue homeostasis, and apoptosis. At the same time, mutations in the genes of glial connexins, as well as a deficiency of these proteins, are associated with such diseases as congenital neuropathies, hearing loss, skin diseases, and brain tumors. This review summarizes the existing data of numerous molecular, electrophysiological, pharmacological, and morphological studies aimed at progress in the study of the physiological and pathophysiological significance of glial and neuronal connexins and GJs for the central nervous system.

摘要

过去20年获得的大量数据表明,成熟中枢神经系统的所有部分,从视网膜和嗅球到脊髓和大脑,都包含通过缝隙连接(GJ)相连的细胞。缝隙连接的形态学基础是一组称为连接子的连接膜半通道,每个连接子的亚基是连接蛋白。在中枢神经系统中,连接蛋白具有特异性,其中某些类型在神经元或神经胶质细胞中表达。神经元的连接蛋白和缝隙连接,结合某些类型的抑制性海马和新皮质神经元集合,提供局部冲动和节律活动的同步、丘脑皮质传导、兴奋性连接的控制,这反映了它们在细胞水平和系统水平的感知、注意力集中和记忆巩固过程中的重要作用。神经胶质细胞的连接蛋白在大脑中普遍表达,由它们形成的缝隙连接提供分子信号传导和代谢合作,并在大脑发育过程中的神经元迁移、髓鞘形成、组织稳态和细胞凋亡过程中发挥一定作用。同时,神经胶质连接蛋白基因的突变以及这些蛋白质的缺乏与先天性神经病、听力丧失、皮肤病和脑肿瘤等疾病有关。本综述总结了众多分子、电生理、药理和形态学研究的现有数据,旨在推进对神经胶质和神经元连接蛋白以及缝隙连接对中枢神经系统的生理和病理生理意义的研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ccb/8432592/cca2fcd57f50/nihms-1737580-f0001.jpg

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