缝隙连接蛋白Connexin43参与神经精神疾病发病机制的研究进展
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摘要
缝隙连接(gap junction,GJ)是细胞间的一种连接形式,主要由缝隙连接蛋白(connexin,Cx)构成。细胞间的物质能量交换通过GJ完成。Cx43蛋白是星形胶质细胞中构成GJ的Cx家族主要成员之一。近些年的研究越来越清晰地阐述了Cx43蛋白的特性及其在神经、肿瘤、心血管等系统疾病发病过程中的重要作用。该文就GJ的结构与功能,Cx43蛋白的编码基因、结构解析、合成、细胞膜定位、调节和在人体中发挥的生理功能,及其在相关神经系统疾病发病进程中的作用等方面的研究成果展开综述。
Gap junction( GJ),which mainly consists of connexins,is a linking method between neighboring cells. Neighboring cells exchange substances,energy and information by gap junction intercellular communication mediated by GJ. Particularly,Cx43 protein is one of the most important members of Cx family.The study in recent years demonstrated the features of Cx43 protein and its important roles in the pathogenesis of neurological disorders,tumors,cardiovascular risks. This article summarizes the structure,functions,coding gene,structure analysis,synthesis,membrane localization,regulation of Cx43. Furthermore,this article explains the physiological functions of Cx43 in human bodies and its important roles in the pathogenesis of related neurological disorders.
Gap junction( GJ),which mainly consists of connexins,is a linking method between neighboring cells. Neighboring cells exchange substances,energy and information by gap junction intercellular communication mediated by GJ. Particularly,Cx43 protein is one of the most important members of Cx family.The study in recent years demonstrated the features of Cx43 protein and its important roles in the pathogenesis of neurological disorders,tumors,cardiovascular risks. This article summarizes the structure,functions,coding gene,structure analysis,synthesis,membrane localization,regulation of Cx43. Furthermore,this article explains the physiological functions of Cx43 in human bodies and its important roles in the pathogenesis of related neurological disorders.
引文
[1] Sarrouilhe D, Dejean C, Mesnil M. Connexin43- and pannexin-based channels in neuroinflammation and cerebral neuropathies[J]. Front Mol Neurosci,2017,10:320.
[2] Condamine S, Lavoie R, Verdier D, et al. Functional rhythmogenic domains defined by astrocytic networks in the trigeminal main sensory nucleus[J]. Glia,2018,66(2):311-26.
[3] 余彬彬, 曹莺. 连接蛋白43与睾丸肿瘤相关性的研究进展[J]. 中华男科学杂志, 2017,23(3):267-70. Yu B B, Cao Y. Correlation of connexin 43 with testicular tumors[J]. Natl J Androl,2017,23(3):267-70.
[4] 朱长良, 裘伟光, 洪涛.缝隙连接及缝隙连接相关疾病研究进展[J]. 重庆医学,2013,42(15):1779-81. Zhu C L, Qiu W G, Hong T. The progression of research about gap junction and gap junction-linked diseases[J]. Chongqing Med, 2013,42(15):1779-81.
[5] Tonkin R S, Bowles C, Perera C J, et al. Attenuation of mechanical pain hypersensitivity by treatment with Peptide5, a connexin-43 mimetic peptide, involves inhibition of NLRP3 inflammasome in nerve-injured mice[J]. Exp Neurol, 2017,300:1-12.
[6] Laird D W, Naus C C, Lampe P D. SnapShot: connexins and disease[J]. Cell, 2017,170(6):1260-1260.e1.
[7] Leybaert L, Lampe P D, Dhein S, et al. Connexins in cardiovascular and neurovascular health and disease: pharmacological implications[J]. Pharmacol Rev, 2017,69(4):396-478.
[8] Scemes E. Nature of plasmalemmal functional “hemichannels”[J]. Biochim Biophys Acta, 2012,1818(8):1880-3.
[9] Clasadonte J, Scemes E, Wang Z, et al. Connexin 43-mediated astroglial metabolic networks contribute to the regulation of the sleep-wake cycle[J]. Neuron, 2017,95(6):1365-80.
[10] Hervé J C, Bourmeyster N, Sarrouilhe D. Diversity in protein-protein interactions of connexins: emerging roles[J]. Biochim Biophys Acta, 2004,1662(1-2):22-41.
[11] Rhett J M, Jourdan J, Gourdie R G. Connexin 43 connexon to gap junction transition is regulated by zonula occludens-1[J]. Mol Biol Cell, 2011,22(9):1516-28.
[12] Orellana J A, Sáez P J, Cortés-Campos C, et al. Glucose increases intracellular free Ca2+ in tanycytes via ATP released through connexin 43 hemichannels[J]. Glia, 2012,60(1):53-68.
[13] Ribeiro-Rodrigues T M, Martins-Marques T, Morel S, et al. Role of connexin 43 in different forms of intercellular communication-gap junctions, extracellular vesicles and tunnelling nanotubes[J]. J Cell Sci, 2017,130(21):3619-30.
[14] Pannasch U, Vargová L, Reingruber J, et al. Astroglial networks scale synaptic activity and plasticity[J]. Proc Natl Acad Sci USA, 2011,108(20):8467-72.
[15] Tencé M, Ezan P, Amigou E, et al. Increased interaction of connexin43 with zonula occludens-1 during inhibition of gap junctions by G protein-coupled receptor agonists[J]. Cell Signal, 2012,24(1):86-98.
[16] Jiang S, Yuan H, Duan L, et al. Glutamate release through connexin 43 by cultured astrocytes in a stimulated hypertonicity model[J]. Brain Res, 2011,1392:8-15.
[17] Hugyecz M, Mracskó E, Hertelendy P, et al. Hydrogen supplemented air inhalation reduces changes of prooxidant enzyme and gap junction protein levels after transient global cerebral ischemia in the rat hippocampus[J]. Brain Res, 2011,1404:31-8.
[18] Baranowska-Bosiacka I, Falkowska A, Gutowska I, et al. Glycogen metabolism in brain and neurons-astrocytes metabolic cooperation can be altered by pre- and neonatal lead (Pb) exposure[J]. Toxicology, 2017,390:146-58.
[19] Gemmel M, Kokras N, Dalla C, et al. Perinatal fluoxetine prevents the effect of pre-gestational maternal stress on 5-HT in the PFC, but maternal stress has enduring effects on mPFC synaptic structure in offspring[J]. Neuropharmacology, 2017,128:168-80.
[20] Giaume C,Theis M. Pharmacological and genetic approaches to study connexin-mediated channels in glial cells of the central nervous system[J]. Brain Res Rev,2010,63(1-2):160-76.
[21] Sun J D,Liu Y,Yuan Y H,et al. Gap junction dysfunction in the prefrontal cortex induces depressive-like behaviors in rats[J]. Neuropsychopharmacology,2012,37(5):1305-20.
[22] Jordan M D,Raos B J,Bunting A S,et al. Human astrocytic grid networks patterned in parylene-C inlayed Si O2trenches[J]. Biomaterials,2016,105:117-26.
[23]李业如,庞祥媚,李敏,等. Cx43对脑胶质瘤C6细胞增殖的影响及机制[J].中国药理学通报,2017,33(7):1008-13. Li Y R,Pang X M,Li M,et al. Effect of Cx43 on proliferation of C6 glioma cells and its mechanisms[J]. Chin Pharmacol Bull,2017,33(7):1008-13.
[24] Jaraíz-Rodríguez M,Tabernero M D,González-Tablas M,et al. A short region of connexin43 reduces human glioma stem cell migration,invasion,and survival through Src,PTEN,and FAK[J].Stem Cell Rep,2017,9(2):451-63.
[2] Condamine S, Lavoie R, Verdier D, et al. Functional rhythmogenic domains defined by astrocytic networks in the trigeminal main sensory nucleus[J]. Glia,2018,66(2):311-26.
[3] 余彬彬, 曹莺. 连接蛋白43与睾丸肿瘤相关性的研究进展[J]. 中华男科学杂志, 2017,23(3):267-70. Yu B B, Cao Y. Correlation of connexin 43 with testicular tumors[J]. Natl J Androl,2017,23(3):267-70.
[4] 朱长良, 裘伟光, 洪涛.缝隙连接及缝隙连接相关疾病研究进展[J]. 重庆医学,2013,42(15):1779-81. Zhu C L, Qiu W G, Hong T. The progression of research about gap junction and gap junction-linked diseases[J]. Chongqing Med, 2013,42(15):1779-81.
[5] Tonkin R S, Bowles C, Perera C J, et al. Attenuation of mechanical pain hypersensitivity by treatment with Peptide5, a connexin-43 mimetic peptide, involves inhibition of NLRP3 inflammasome in nerve-injured mice[J]. Exp Neurol, 2017,300:1-12.
[6] Laird D W, Naus C C, Lampe P D. SnapShot: connexins and disease[J]. Cell, 2017,170(6):1260-1260.e1.
[7] Leybaert L, Lampe P D, Dhein S, et al. Connexins in cardiovascular and neurovascular health and disease: pharmacological implications[J]. Pharmacol Rev, 2017,69(4):396-478.
[8] Scemes E. Nature of plasmalemmal functional “hemichannels”[J]. Biochim Biophys Acta, 2012,1818(8):1880-3.
[9] Clasadonte J, Scemes E, Wang Z, et al. Connexin 43-mediated astroglial metabolic networks contribute to the regulation of the sleep-wake cycle[J]. Neuron, 2017,95(6):1365-80.
[10] Hervé J C, Bourmeyster N, Sarrouilhe D. Diversity in protein-protein interactions of connexins: emerging roles[J]. Biochim Biophys Acta, 2004,1662(1-2):22-41.
[11] Rhett J M, Jourdan J, Gourdie R G. Connexin 43 connexon to gap junction transition is regulated by zonula occludens-1[J]. Mol Biol Cell, 2011,22(9):1516-28.
[12] Orellana J A, Sáez P J, Cortés-Campos C, et al. Glucose increases intracellular free Ca2+ in tanycytes via ATP released through connexin 43 hemichannels[J]. Glia, 2012,60(1):53-68.
[13] Ribeiro-Rodrigues T M, Martins-Marques T, Morel S, et al. Role of connexin 43 in different forms of intercellular communication-gap junctions, extracellular vesicles and tunnelling nanotubes[J]. J Cell Sci, 2017,130(21):3619-30.
[14] Pannasch U, Vargová L, Reingruber J, et al. Astroglial networks scale synaptic activity and plasticity[J]. Proc Natl Acad Sci USA, 2011,108(20):8467-72.
[15] Tencé M, Ezan P, Amigou E, et al. Increased interaction of connexin43 with zonula occludens-1 during inhibition of gap junctions by G protein-coupled receptor agonists[J]. Cell Signal, 2012,24(1):86-98.
[16] Jiang S, Yuan H, Duan L, et al. Glutamate release through connexin 43 by cultured astrocytes in a stimulated hypertonicity model[J]. Brain Res, 2011,1392:8-15.
[17] Hugyecz M, Mracskó E, Hertelendy P, et al. Hydrogen supplemented air inhalation reduces changes of prooxidant enzyme and gap junction protein levels after transient global cerebral ischemia in the rat hippocampus[J]. Brain Res, 2011,1404:31-8.
[18] Baranowska-Bosiacka I, Falkowska A, Gutowska I, et al. Glycogen metabolism in brain and neurons-astrocytes metabolic cooperation can be altered by pre- and neonatal lead (Pb) exposure[J]. Toxicology, 2017,390:146-58.
[19] Gemmel M, Kokras N, Dalla C, et al. Perinatal fluoxetine prevents the effect of pre-gestational maternal stress on 5-HT in the PFC, but maternal stress has enduring effects on mPFC synaptic structure in offspring[J]. Neuropharmacology, 2017,128:168-80.
[20] Giaume C,Theis M. Pharmacological and genetic approaches to study connexin-mediated channels in glial cells of the central nervous system[J]. Brain Res Rev,2010,63(1-2):160-76.
[21] Sun J D,Liu Y,Yuan Y H,et al. Gap junction dysfunction in the prefrontal cortex induces depressive-like behaviors in rats[J]. Neuropsychopharmacology,2012,37(5):1305-20.
[22] Jordan M D,Raos B J,Bunting A S,et al. Human astrocytic grid networks patterned in parylene-C inlayed Si O2trenches[J]. Biomaterials,2016,105:117-26.
[23]李业如,庞祥媚,李敏,等. Cx43对脑胶质瘤C6细胞增殖的影响及机制[J].中国药理学通报,2017,33(7):1008-13. Li Y R,Pang X M,Li M,et al. Effect of Cx43 on proliferation of C6 glioma cells and its mechanisms[J]. Chin Pharmacol Bull,2017,33(7):1008-13.
[24] Jaraíz-Rodríguez M,Tabernero M D,González-Tablas M,et al. A short region of connexin43 reduces human glioma stem cell migration,invasion,and survival through Src,PTEN,and FAK[J].Stem Cell Rep,2017,9(2):451-63.