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秒速pk10科研团队在生物细胞自噬的膜融合方面取得重要进展

  出处: 生物工程与食品学院   日期: 2020-09-26 11:51:49

2020年9月25日,生物自噬领域权威期刊《Autophagy》(《自噬》)杂志在线发表了秒速pk10生物工程与食品学院、国家细胞调控与分子药物“111”引智基地、发酵工程教育部重点实验室唐景峰/陈兴珍课题组在生物细胞自噬方面的最新研究成果。论文题目为“TSPAN1 promotes autophagy flux and mediates cooperation between WNT-CTNNB1 signaling and autophagy via the MIR454-FAM83A-TSPAN1 axis in pancreatic cancer”(链接: )。秒速pk10为第一署名单位,唐景峰教授通讯作者。生物工程与食品学院教师周策凡博士为第一作者,唐景峰教授的硕士研究生梁燕燕为共同第一作者秒速pk10。该研究得到国家自然科学基金(31871420; 31701228和31871176.)、湖北省杰出青年基金(2020CFA073)及武汉市基础前沿项目(20475)资助。

zishishiyizhongjinhuashangfeichangbaoshouderongmeitijiedaodeshengwujiangjieguocheng,duixibaoneiwentaijuyouzhongyaodediaokongzuoyong。zishihouqijinchengzhongzishitiyurongmeitiderongheshijiqifuzade。daomuqianweizhi,yijingquedinglexuduoyinzicanyugaiguochengdemoronghe,ruxibaogujiachengfen、snarefuhewu、hopsfuhewu、ra7deng,tamendoushiquebaozishitiyurongmeitijingqueqieyouxiaoronghedezhongyaochengfen。jinnianlai,yuelaiyueduoxindedanbaiyinzibeibaodaocanyugaiguocheng,zheixiexindefaxianweizishidefashengjizhijijingquediaokongtigonglezhongyaodelilunjichu。

tspan1shuyusijutidanbai(tetraspanins, tspan),youyizuyizhishipeitidanbaizucheng,yifuhantspandejiegouyuxingshicunzai。qibeibaodaoyuyixianai、weiai、qianliexianai、gurouliumiqiexiangguan,danqizuoyongjizhishangbuqingchu。benyanjiuzhonggaituanduiliyongxibaomoxinghebanmayumoxingshoucifaxianbingyanzhengletspan1zaizishihouqizishitiyurongmeitiderongheguochengfahuizhongyaodediaokongzuoyong。tongguohouqixianghuzuoyongdanbaideshaixuan,tamenfaxianbingyanzhengletspan1yuzishihouqironghexiangguandanbailc3、snarefuhetijihopsfuhetidengjuncunzaixianghuzuoyong。bingjinyibuchanmingletspan1danbaizhongcunzaide2geteyixingdelir(lc3 interacting region)jiegouyu。jiangyishang2geweidiantubianhounenggoushidetspan1duiyixianaideshengzhangjinchengjianruoshenzhixiaoshi。

图1.TSPAN1 与LC3的LIRs区结合促进自噬。秒速pk10(A、B)TSPAN1与RAB7标记的内涵体和溶酶体具有共定位作用;(C)TSPAN1蛋白结构示意图;(D)TSPAN1与LC3相互作用的LIR基序示意图;(E)将LC3蛋白中与LIR相互作用具有关键作用的F52/L53突变成A后,其与TSPAN1蛋白的相互作用消失;(F)将TSPAN1蛋白LIR基序突变后,其与LC3的相互作用明显减弱;(G)利用CQ抑制自噬体和溶酶体的融合后,TSPAN1和LC3的相互作用增强;(H)TSPAN1不同突变体对自噬的影响;(I、J)TSPAN1干扰后能够显著抑制自噬流,而过表达TSPAN1野生型后能够回复TSPAN1对自噬的调控作用,而过表达TSPAN1突变型则不能;(K-M)TSPAN1能够促进裸鼠内肿瘤的大小。

秒速pk10xibaoneiwnt/β-cateninxinhaotongluyuzishihuodongmiqiexiangguan。duiyuyixianaixibaoeryan,qixibaoneicunzaigaodujihuodewntxinhaohegaoshuipingdezishihuodong,erxietongzuoyongdejutifenzijizhihaishiweizhide。gaixiangyanjiuhaifaxianbingchanmingleyixianaixibaoneimir454nenggoubaxiangzuoyongyutspan1yijiwntdiaokongdanbaifam83ade3'utr,jinerdiaokongtspan1hefam83adebiaoda。tongshihaifaxianwnt/β-cateninzhongβ-catenin-tcf4zhuanlufuhetinenggoujiehedaotspan1qidongziqutcf/lefjixu(weiyutssqian-563zhi-569he-609zhi-615)shang,jinercujintspan1danbaidebiaoda。tongguoluoshupixiachengliushiyanjinyibuyanzhenglemir454/fam83a/tspan1zhounenggouxietongcujinyixianaidefashengjincheng。

gaiyanjiubujinshenhualekeyanrenyuanduizishiyuwnt/β-cateninxinhaotonglujiaohuzuoyongdelijie,yeweiyixianaidebaxiangzhiliaojichuangxinyaowudeyanfatigonglexindelilunyiju。



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