Tropomyosin isoform 5b is expressed in human erythrocytes: implications of tropomodulin-TM5 or tropomodulin-TM5b complexes in the protofilament and hexagonal organization of membrane skeletons

作     者：Sung, LA Gao, KM Yee, LJ Temm-Grove, CJ Helfman, DM Lin, JJC Mehrpouryan, M 

作者机构：Univ Calif San Diego Dept Bioengn La Jolla CA 92093 USA Univ Calif San Diego Ctr Genet Mol La Jolla CA 92093 USA Univ Arizona Dept Nutr Sci Tucson AZ 85721 USA Cold Spring Harbor Lab Cold Spring Harbor NY 11724 USA Univ Iowa Dept Biol Sci Iowa City IA 52242 USA 

出 版 物：《BLOOD》 (血液)

年 卷 期：2000年第95卷第4期

页      面：1473-1480页

核心收录：

学科分类：1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 10[医学] 

基　　金：NHLBI NIH HHS [HL43026] Funding Source: Medline NICHD NIH HHS [HD18577] Funding Source: Medline NIDDK NIH HHS [DK47673] Funding Source: Medline 

主　　题：氨基酸序列 载体蛋白质类/血液 载体蛋白质类/化学 克隆 分子 细胞骨架/超微结构 红细胞膜/超微结构 红细胞/代谢 红系祖细胞/代谢 红系祖细胞/超微结构 微丝蛋白质类/血液 微丝蛋白质类/化学 分子序列数据 蛋白质亚型/血液 蛋白质亚型/化学 蛋白质亚型/遗传学 重组蛋白质类/化学 重组蛋白质类/代谢 序列比对 序列同源性 氨基酸 原肌球调节蛋白质 原肌球蛋白/血液 原肌球蛋白/化学 原肌球蛋白/遗传学 动物 人类 大鼠 

摘      要：The human erythrocyte membrane skeleton consists of hexagonal lattices with junctional complexes containing F-actin protofilaments of approximately 33-37 nm in length. We hypothesize that complexes formed by tropomodulin, a globular capping protein at the pointed end of actin filaments, and tropomyosin (TM), a rod-like molecule of approximately 33-35 nm, may contribute to the formation of protofilaments, We have previously cloned the human tropomodulin complementary DNA and identified human TM isoform 5 (hTM5), a product of the gamma-TM gene, as one of the major TM isoforms in erythrocytes, We now identify TM5b, a product of the alpha-TM gene, to-be the second major TM isoform, TM5a, the alternatively spliced isoform of the (U-TM gene, which differs by 1 exon and has a weaker actin-binding affinity, however, is not present. TM4, encoded by the delta-TM gene, is not present either. In sodium dodecyl sulfate-polyacrylamide gel electrophoresis, hTM5 comigrated with the slower TM major species in erythrocyte membranes, and hTM5b comigrated with the faster TM major species. TM5b, like TM5, binds strongly to tropomodulin, more so than other TM isoforms, The 2 major TM isoforms, therefore, share several common features: They have 248 residues, are approximately 33-35 nm long, and have high affinities toward F-actin and tropomodulin. These common features may be the key to the mechanism by which protofilaments are formed. Tropomodulin-TM5 or tropomodulin-TM5b complexes may stabilize F-actin in segments of approximately 33-37 nm during erythroid terminal differentiation and may, therefore, function as a molecular ruler. TM5 and TM5b further define the hexagonal geometry of the skeletal network and allow actin-regulatory functions of TMs to be modulated by tropomodulin, (C) 2000 by The American Society of Hematology.