通过使用美国国立生物技术信息中心(National Center for Biotechnology Information,NCBI)数据库检索出斑马鱼Smyd1a蛋白的氨基酸序列信息,对其进行生理生化分析,并通过NBCI寻找同源性高的不同种属的序列构建系统发育树。结果显示:Smy...通过使用美国国立生物技术信息中心(National Center for Biotechnology Information,NCBI)数据库检索出斑马鱼Smyd1a蛋白的氨基酸序列信息,对其进行生理生化分析,并通过NBCI寻找同源性高的不同种属的序列构建系统发育树。结果显示:Smyd1a蛋白的氨基酸数量是489个,分子量是56376.54 Da,理论等电点是6.27;该蛋白中,谷氨酸(Glu)含量最高,为8.4%;其次是亮氨酸(Leu)和丙氨酸(Ala),分别为8.0%和7.0%。Smyd1a是一个亲水蛋白质,但不是一个分泌蛋白,不存在跨膜螺旋区域,存在蛋白质的无规则卷曲等构象,Smyd1a属于SET家族。展开更多
Skeletal and cardiac muscles are striated myofibers that contain highly organized sarcomeres for muscle contraction.Recent studies revealed that Smyd1,a lysine methyltransferase,plays a key role in sarcomere assembly ...Skeletal and cardiac muscles are striated myofibers that contain highly organized sarcomeres for muscle contraction.Recent studies revealed that Smyd1,a lysine methyltransferase,plays a key role in sarcomere assembly in heart and trunk skeletal muscles.However,Smyd1 expression and function in craniofacial muscles are not known.Here,we analyze the developmental expression and function of two smyd1 paralogous genes,smyd1 a and smyd1 b,in craniofacial and cardiac muscles of zebrafish embryos.Our data show that loss of smyd1a(smyd1a^(mb5))or smyd1b(smyd1b^(sa15678))has no visible effects on myogenic commitment and expression of myod and myosin heavy-chain m RNA transcripts in craniofacial muscles.However,myosin heavy-chain protein accumulation and sarcomere organization are dramatically reduced in smyd1b^(sa15678) single mutant,and almost completely diminish in smyd1a^(mb5);smyd1b^(sa15678) double mutant,but not in smyd1a^(mb5) mutant.Similar defects are also observed in cardiac muscles of smyd1b^(sa15678) mutant.Defective craniofacial and cardiac muscle formation is associated with an upregulation of hsp90α1 and unc45b mRNA expression in smyd1b^(sa15678) and smyd1a^(mb5);smyd1b^(sa15678) mutants.Together,our studies indicate that Smyd1b,but not Smyd1a,plays a key role in myosin heavy-chain protein expression and sarcomere organization in craniofacial and cardiac muscles.Loss of smyd1b results in muscle-specific stress response.展开更多
组蛋白甲基转移酶1(SET and MYND domain containing 1,Smyd1)是组蛋白赖氨酸甲基转移酶SMYD家族成员,其表达具有肌组织特异性,可通过甲基化组蛋白和非组蛋白,在转录水平调控靶基因表达,参与细胞结构组成和生理活动。研究发现,Smyd1是...组蛋白甲基转移酶1(SET and MYND domain containing 1,Smyd1)是组蛋白赖氨酸甲基转移酶SMYD家族成员,其表达具有肌组织特异性,可通过甲基化组蛋白和非组蛋白,在转录水平调控靶基因表达,参与细胞结构组成和生理活动。研究发现,Smyd1是调节心脏和骨骼肌发育的关键因子之一,在肌节组装、肌细胞生长和线粒体能量代谢等过程中发挥重要生物学作用,其表达异常与多种心脏和骨骼肌疾病的发生发展密切相关。运动可促进心脏和骨骼肌生长发育和功能改善,同时调节正常生理和病理条件下Smyd1表达。Smyd1是否可作为运动作用的靶点,通过调控其下游分子和表观遗传改变,参与运动效应值得研究。本文对近年来Smyd1的生物学表征及其在心脏和骨骼肌发育和成体功能维持中的作用进行梳理,对其运动干预效应进行总结和展望,以期为临床心脏和骨骼肌疾病的治疗靶点及运动训练和康复干预的作用靶点筛选研究提供理论依据。展开更多
文摘通过使用美国国立生物技术信息中心(National Center for Biotechnology Information,NCBI)数据库检索出斑马鱼Smyd1a蛋白的氨基酸序列信息,对其进行生理生化分析,并通过NBCI寻找同源性高的不同种属的序列构建系统发育树。结果显示:Smyd1a蛋白的氨基酸数量是489个,分子量是56376.54 Da,理论等电点是6.27;该蛋白中,谷氨酸(Glu)含量最高,为8.4%;其次是亮氨酸(Leu)和丙氨酸(Ala),分别为8.0%和7.0%。Smyd1a是一个亲水蛋白质,但不是一个分泌蛋白,不存在跨膜螺旋区域,存在蛋白质的无规则卷曲等构象,Smyd1a属于SET家族。
基金supported by funding from the U.S.National Institute of Health(NIH)National Institute of Arthritis and Musculoskeletal and Skin Diseases(R01AR072703 to S.Du)supported in part by fellowships from the China Scholarship Council。
文摘Skeletal and cardiac muscles are striated myofibers that contain highly organized sarcomeres for muscle contraction.Recent studies revealed that Smyd1,a lysine methyltransferase,plays a key role in sarcomere assembly in heart and trunk skeletal muscles.However,Smyd1 expression and function in craniofacial muscles are not known.Here,we analyze the developmental expression and function of two smyd1 paralogous genes,smyd1 a and smyd1 b,in craniofacial and cardiac muscles of zebrafish embryos.Our data show that loss of smyd1a(smyd1a^(mb5))or smyd1b(smyd1b^(sa15678))has no visible effects on myogenic commitment and expression of myod and myosin heavy-chain m RNA transcripts in craniofacial muscles.However,myosin heavy-chain protein accumulation and sarcomere organization are dramatically reduced in smyd1b^(sa15678) single mutant,and almost completely diminish in smyd1a^(mb5);smyd1b^(sa15678) double mutant,but not in smyd1a^(mb5) mutant.Similar defects are also observed in cardiac muscles of smyd1b^(sa15678) mutant.Defective craniofacial and cardiac muscle formation is associated with an upregulation of hsp90α1 and unc45b mRNA expression in smyd1b^(sa15678) and smyd1a^(mb5);smyd1b^(sa15678) mutants.Together,our studies indicate that Smyd1b,but not Smyd1a,plays a key role in myosin heavy-chain protein expression and sarcomere organization in craniofacial and cardiac muscles.Loss of smyd1b results in muscle-specific stress response.
文摘组蛋白甲基转移酶1(SET and MYND domain containing 1,Smyd1)是组蛋白赖氨酸甲基转移酶SMYD家族成员,其表达具有肌组织特异性,可通过甲基化组蛋白和非组蛋白,在转录水平调控靶基因表达,参与细胞结构组成和生理活动。研究发现,Smyd1是调节心脏和骨骼肌发育的关键因子之一,在肌节组装、肌细胞生长和线粒体能量代谢等过程中发挥重要生物学作用,其表达异常与多种心脏和骨骼肌疾病的发生发展密切相关。运动可促进心脏和骨骼肌生长发育和功能改善,同时调节正常生理和病理条件下Smyd1表达。Smyd1是否可作为运动作用的靶点,通过调控其下游分子和表观遗传改变,参与运动效应值得研究。本文对近年来Smyd1的生物学表征及其在心脏和骨骼肌发育和成体功能维持中的作用进行梳理,对其运动干预效应进行总结和展望,以期为临床心脏和骨骼肌疾病的治疗靶点及运动训练和康复干预的作用靶点筛选研究提供理论依据。
