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作 者:周金武[1] 程肖蕊[1] 周文霞[1] 张永祥[1]
机构地区:[1]军事医学科学院毒物药物研究所,北京100850
出 处:《生命科学》2009年第4期517-523,共7页Chinese Bulletin of Life Sciences
基 金:国家自然科学基金项目(90709012;30772562;30600760);国家重点基础研究发展计划"973"项目(2004CB518907);国家高技术研究与发展计划"863"项目(2007AA02Z400)
摘 要:Reticulons(RTNs)蛋白是一类广泛存在于真菌、植物及动物等真核生物的膜蛋白,主要定位于内质网,尤其是管状内质网,原核生物中至今尚未发现其同系物。哺乳动物基因组中有RTN1、RTN2、RTN3及RTN4共四类相互独立的基因,因启动子及选择性剪接方式不同每个基因可产生不同转录本。RTNs家族成员氨基端序列高度可变且大小显著不同,羧基端的约200个氨基酸残基则高度保守,被称为内质网蛋白同源结构域(reticulon-homology domain,RHD)。RTNs高度可变的氨基端赋予其各成员物种特异性及细胞特异性的功能,羧基端的RHD则是其执行基本细胞功能的基础。越来越多的研究结果表明,RTNs可参与蛋白转运、参与膜结构形态发生或稳定及细胞分裂、构成内质网膜通道或转运体、调节细胞凋亡、调节β分泌酶(β-site APP cleaving enzyme1,BACE1)活性及抑制神经再生等。该文就RTNs家族各成员基因和蛋白的结构特性以及功能特点的研究进展进行简要综述。Reticulons(RTNs), predominantly associated with endoplasmic reticulumare(ER), especially tubular ER, widely exist as a family of membrane-bound proteins in eukaryotic organisms including fungi, plants and animals, but no homologues have been identified in prokaryotes so far. There are four independent RTN genes, such as RTN1, RTN2, RTN3 and RTN4 in mamalian genome, and each of them produces a range of transcripts due to deferential promoter usage and/or alternative splicing. All RTNs share a highly conserved C-terminal reticulon homology domain(RHD) of 200 or so amino-acid residues whereas the N-terminal regions are highly variable in sequence and length. It is the variability in N-terminus and the conservation in C-terminus of RTNs that confers species/cell-specific functions and a common cellular fuction to each member respectively. Many studies indicated that RTNs participate in protein trafficking and membrane strctural morphogenesis or stabilization, play a role in cell division, form channels or transportors in ER, regulate apoptosis, modulate BACE1 negatively, inhibit neuron regeneration and so on. So this review focuses on the recent progress in the structure and functions of RTN genes and proteins.
关 键 词:reticulons(RTNs) 拓朴结构 蛋白转运 Β分泌酶 神经再生
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