Engineered Cx26 variants established functional heterotypic Cx26/Cx43 and Cx26/Cx40 gap junction channels.
作者： Levent B. Karademir , Hiroshi Aoyama , Benny Yue , Honghong Chen , Donglin Bai
DOI: 10.1042/BCJ20160200
关键词:
摘要: Gap junction (GJ) channels mediate direct intercellular communication and are composed of two docked hemichannels (connexin oligomers). It is well documented that the docking formation GJs possible only between compatible (or connexins). The mechanisms heterotypic compatibility not fully clear. We aligned protein sequences docking-compatible -incompatible connexins with connexin26 (Cx26). found hydrogen bond (HB)-forming residues on second extracellular domain (E2) Cx26 their equivalent conserved within connexins, but different docking-incompatible connexins. Replacing one or both these into corresponding in incompatible (K168V, N176H K168V-N176H) increased morphological functional connexin43 (Cx43) connexin40 (Cx40), indicating important for incompatibility Our homology structure models predict HBs hydrophobic interactions at E2 interface K168V-N176H/Cx43 probably other Revealing key will assist us understanding why putative hotspots disease-linked mutants.
portlandpress.com
biochemj.org参考文章(51)
Hassan Musa, Edward Fenn, Mark Crye, Joanna Gemel, Eric C Beyer, Richard D Veenstra, None, Amino terminal glutamate residues confer spermine sensitivity and affect voltage gating and channel conductance of rat connexin40 gap junctions. The Journal of Physiology. ,vol. 557, pp. 863- 878 ,(2004) , 10.1113/JPHYSIOL.2003.059386
Xiaoling Tong, Hiroshi Aoyama, Tomitake Tsukihara, Donglin Bai, Charge at the 46th residue of connexin 50 is crucial for the gap-junctional unitary conductance and transjunctional voltage-dependent gating. The Journal of Physiology. ,vol. 592, pp. 5187- 5202 ,(2014) , 10.1113/JPHYSIOL.2014.280636
Mark Yeager, Bruce J. Nicholson, Structure and biochemistry of gap junctions Advances in Molecular and Cell Biology. ,vol. 30, pp. 31- 98 ,(2000) , 10.1016/S1569-2558(00)30003-0
Patrik Schadzek, Barbara Schlingmann, Frank Schaarschmidt, Julia Lindner, Michael Koval, Alexander Heisterkamp, Matthias Preller, Anaclet Ngezahayo, The cataract related mutation N188T in human connexin46 (hCx46) revealed a critical role for residue N188 in the docking process of gap junction channels Biochimica et Biophysica Acta. ,vol. 1858, pp. 57- 66 ,(2016) , 10.1016/J.BBAMEM.2015.10.001
P Primignani, P Castorina, F Sironi, C Curcio, U Ambrosetti, DA Coviello, A novel dominant missense mutation--D179N--in the GJB2 gene (Connexin 26) associated with non-syndromic hearing loss. Clinical Genetics. ,vol. 63, pp. 516- 521 ,(2003) , 10.1034/J.1399-0004.2003.00079.X
Laura M Magnotti, Daniel A Goodenough, David L Paul, None, Functional heterotypic interactions between astrocyte and oligodendrocyte connexins. Glia. ,vol. 59, pp. 26- 34 ,(2011) , 10.1002/GLIA.21073
Isaac E. García, Jaime Maripillán, Oscar Jara, Ricardo Ceriani, Angelina Palacios-Muñoz, Jayalakshmi Ramachandran, Pablo Olivero, Tomas Perez-Acle, Carlos González, Juan C. Sáez, Jorge E. Contreras, Agustín D. Martínez, Keratitis-Ichthyosis-Deafness Syndrome-Associated Cx26 Mutants Produce Nonfunctional Gap Junctions but Hyperactive Hemichannels When Co-Expressed With Wild Type Cx43 Journal of Investigative Dermatology. ,vol. 135, pp. 1338- 1347 ,(2015) , 10.1038/JID.2015.20
G. Sosinsky, Mixing of connexins in gap junction membrane channels Proceedings of the National Academy of Sciences of the United States of America. ,vol. 92, pp. 9210- 9214 ,(1995) , 10.1073/PNAS.92.20.9210
So Nakagawa, Xiang-Qun Gong, Shoji Maeda, Yuhua Dong, Yuko Misumi, Tomitake Tsukihara, Donglin Bai, Asparagine 175 of Connexin32 Is a Critical Residue for Docking and Forming Functional Heterotypic Gap Junction Channels with Connexin26 Journal of Biological Chemistry. ,vol. 286, pp. 19672- 19681 ,(2011) , 10.1074/JBC.M110.204958
S Haubrich, H J Schwarz, F Bukauskas, H Lichtenberg-Fraté, O Traub, R Weingart, K Willecke, Incompatibility of connexin 40 and 43 Hemichannels in gap junctions between mammalian cells is determined by intracellular domains. Molecular Biology of the Cell. ,vol. 7, pp. 1995- 2006 ,(1996) , 10.1091/MBC.7.12.1995