Roginski Raymond S, Lau Chi W, Santoiemma Phillip P, Weaver Sara J, Du Peicheng, Soteropoulos Patricia, Yang Jay
Department of Anesthesiology, CMC VA Medical Center, Philadelphia, PA 19104, United States; Department of Anesthesiology and Critical Care, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, United States.
Department of Anesthesiology, CMC VA Medical Center, Philadelphia, PA 19104, United States.
Gene. 2018 Mar 30;648:42-53. doi: 10.1016/j.gene.2018.01.029. Epub 2018 Jan 12.
The known functions of the human GCOM1 complex hub gene include transcription elongation and the intercalated disk of cardiac myocytes. However, in all likelihood, the gene's most interesting, and thus far least understood, roles will be found in the central nervous system. To investigate the functions of the GCOM1 gene in the CNS, we have cloned human and rat brain cDNAs encoding novel, 105 kDa GCOM1 combined (Gcom) proteins, designated Gcom15, and identified a new group of GCOM1 interacting genes, termed Gints, from yeast two-hybrid (Y2H) screens. We showed that Gcom15 interacts with the NR1 subunit of the NMDA receptor by co-expression in heterologous cells, in which we observed bi-directional co-immunoprecipitation of human Gcom15 and murine NR1. Our Y2H screens revealed 27 novel GCOM1 interacting genes, many of which are synaptic proteins and/or play roles in neurologic diseases. Finally, we showed, using rat brain protein preparations, that the Gint internexin-alpha (INA), a known interactor of the NMDAR, co-IPs with GCOM1 proteins, suggesting a GCOM1-GRIN1-INA interaction and a novel pathway that may be relevant to neuroprotection.
人类GCOM1复合中心基因的已知功能包括转录延伸和心肌细胞的闰盘。然而，很有可能，该基因最有趣且迄今为止了解最少的作用将在中枢神经系统中被发现。为了研究GCOM1基因在中枢神经系统中的功能，我们克隆了编码新型105 kDa GCOM1复合（Gcom）蛋白（命名为Gcom15）的人类和大鼠脑cDNA，并通过酵母双杂交（Y2H）筛选鉴定了一组新的GCOM1相互作用基因，称为Gints。我们通过在异源细胞中共表达表明Gcom15与NMDA受体的NR1亚基相互作用，在其中我们观察到人类Gcom15和小鼠NR1的双向共免疫沉淀。我们的Y2H筛选揭示了27个新的GCOM1相互作用基因，其中许多是突触蛋白和/或在神经疾病中起作用。最后，我们使用大鼠脑蛋白制剂表明，已知的NMDAR相互作用蛋白Gint中间丝蛋白α（INA）与GCOM1蛋白进行共免疫沉淀，提示GCOM1 - GRIN1 - INA相互作用以及一条可能与神经保护相关的新途径。
