Nano Letters封面 :北大王世强组揭示控制心脏收缩功能的重要分子机制,为认识和治疗心脏疾病提供了新理论、新思路

2020-09-16 北大生科 Bio生物世界

2020年9月9日,著名的纳米科学期刊 Nano Letters 以封面故事发表了北京大学王世强教授实验室与斯坦福大学崔便晓教授实验室合作的研究论文。为认识和治疗心脏疾病提供了新理论、新思路。

2020年9月9日,著名的纳米科学期刊 Nano Letters 以封面故事发表了北京大学王世强教授实验室与斯坦福大学崔便晓教授实验室合作的研究论文:Nanobar array assay revealed complementary roles of BIN1 splice isoforms in cardiac T-tubule morphogenesis 。报道了他们的新发现:含有和不含磷酸肌醇结合域的两种BIN1剪切体通过功能互补的结构互作形成心肌细胞整齐排列的横管膜结构。

横管形态发生和定位的嵌合BIN1模型

Nano Letters 封面图片展示了横管形态发生和定位的嵌合BIN1(comboBIN1)模型。其中银色结构代表肌原纤维,黄色结构代表肌小节间的Z盘,白色结构代表能成管(但不能定位)的pBIN1,红色结构代表能定位于Z盘uBIN1。图示功能互补的pBIN1与uBIN1相互作用,形成了沿Z盘定位的横管膜系统。该封面图片由最早启动该课题的论文作者、2004级研究生吴昊迪博士绘制。

心肌细胞的横管膜与肌质网膜平行排列,二者之间的钙信号耦联决定着心脏的泵血能力。横管膜形态异常与多数心脏疾病密切相关。然而横管膜形态发生与定位的分子机制一直未能阐明。

BIN1是一类具有香蕉形曲率的蛋白质分子。王世强教授的博士生韩晶、李琳琳、郭前进、梁景辉等同学在心肌细胞首次鉴定出带有磷酸肌醇结合域的BIN1剪切体pBIN1,并发现其表达产物会诱导新生鼠心肌细胞产生大量杂乱无章的管状膜结构。相反,缺少磷酸肌醇结合域的剪切体uBIN1表达于心肌细胞Z盘结构,但不能形成管状结构。

为了弄清不同BIN1剪切体的分子性质,王世强教授实验室与斯坦福大学崔便晓教授实验室合作,在硅芯片上设计了具有不同曲率的条状纳米结构,并在其上培养表达不同BIN1剪切体的细胞。结果表明,pBIN1富集于高曲率的纳米条两端,而uBIN1弥散于细胞质。惊奇的是当两类剪切体共表达时,uBIN1被pBIN1募集到纳米条高曲率的两端,而uBIN也能将pBIN1形成的管状膜结构铆定到心肌细胞的Z盘。

作者们由此提出了横管膜形态发生和定位的comboBIN1理论:pBIN1通过与磷酸肌醇的结合组织细胞膜泡形成横管膜,并通过与uBIN的嵌合由uBIN1的SH3结构域铆定于Z盘,形成与肌质网的结构耦联。

根据这一理论,pBIN1与uBIN1的剪切失衡将导致横管结构和功能异常,这一点在心肌梗塞模型中得到验证。相反,在心肌特异性过表达uBIN1的大鼠中,心肌梗塞对横管的影响较小,心脏收缩功能显着改善。

因此,上述发现不仅揭示了控制心脏收缩功能的重要分子机制,也为认识和治疗心脏疾病提供了新理论、新思路。

原始出处:

Lin-Lin Li, Qian-Jin Guo, Hsin-Ya Lou,et al.Nanobar Array Assay Revealed Complementary Roles of BIN1 Splice Isoforms in Cardiac T-Tubule Morphogenesis.Nano Lett. 2020 Sep 9;20(9):6387-6395. doi: 10.1021/acs.nanolett.0c01957. Epub 2020 Aug 10.

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    2021-02-14 anminleiryan
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    2021-08-13 晓辰
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    2020-09-25 咻凡

    控制心脏收缩功能的重要分子机制,为认识和治疗心脏疾病提供了新理论、新思路

    0

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    2020-09-24 Lexi

    在心肌特异性过表达uBIN1的大鼠中,心肌梗塞对横管的影响较小,心脏收缩功能显着改善。

    0

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  8. [GetPortalCommentsPageByObjectIdResponse(id=1878351, encodeId=df6b18e8351ad, content=<a href='/topic/show?id=c157696175' target=_blank style='color:#2F92EE;'>#ERS#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=6961, encryptionId=c157696175, topicName=ERS)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e93e105, createdName=anminleiryan, createdTime=Sun Feb 14 00:38:55 CST 2021, time=2021-02-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2019368, encodeId=8074201936867, content=<a href='/topic/show?id=61f458359f7' target=_blank style='color:#2F92EE;'>#新思路#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=58359, encryptionId=61f458359f7, topicName=新思路)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=a5712500001, createdName=晓辰, createdTime=Fri Aug 13 13:38:55 CST 2021, time=2021-08-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1814772, encodeId=25621814e7275, content=<a href='/topic/show?id=479d96059ae' target=_blank style='color:#2F92EE;'>#重要分子#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=96059, encryptionId=479d96059ae, topicName=重要分子)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=ed25376, createdName=gdsun, createdTime=Sat Jul 03 03:38:55 CST 2021, time=2021-07-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2038419, encodeId=e5342038419a0, content=<a href='/topic/show?id=f7c61e90472' target=_blank style='color:#2F92EE;'>#TTE#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=17904, encryptionId=f7c61e90472, topicName=TTE)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=96f62500201, createdName=12498e67m28暂无昵称, createdTime=Wed Jul 21 12:38:55 CST 2021, time=2021-07-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=888246, encodeId=12ef88824691, content=控制心脏收缩功能的重要分子机制,为认识和治疗心脏疾病提供了新理论、新思路, beContent=null, objectType=article, channel=null, level=null, likeNumber=92, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=b58d5402080, createdName=咻凡, createdTime=Fri Sep 25 11:42:21 CST 2020, time=2020-09-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=887954, encodeId=9c8888e95408, content=在心肌特异性过表达uBIN1的大鼠中,心肌梗塞对横管的影响较小,心脏收缩功能显着改善。, beContent=null, objectType=article, channel=null, level=null, likeNumber=86, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=ae205385871, createdName=Lexi, createdTime=Thu Sep 24 14:17:00 CST 2020, time=2020-09-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1395373, encodeId=cbf213953e35c, content=<a href='/topic/show?id=562b51588e6' target=_blank style='color:#2F92EE;'>#心脏疾病#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=51588, encryptionId=562b51588e6, topicName=心脏疾病)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=49022500195, createdName=12498e0fm78暂无昵称, createdTime=Fri Sep 18 06:38:55 CST 2020, time=2020-09-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1039324, encodeId=bc15103932413, content=机制研究离临床仍然有距离,不过与临床结合思考,仍然有帮助的,不能仅仅是纯临床思维,转化思维同样重要, beContent=null, objectType=article, channel=null, level=null, likeNumber=45, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=肿肿, createdTime=Wed Sep 16 18:38:55 CST 2020, time=2020-09-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=885817, encodeId=6a5a88581ef5, content=厉害,越来越好, beContent=null, objectType=article, channel=null, level=null, likeNumber=85, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20220301/6252e946e5ef413b86dc0f7d1f73b6db/9a7e8c88a38e487b8da4968a67bbd261.png, createdBy=b9f692910, createdName=rayms, createdTime=Wed Sep 16 17:03:04 CST 2020, time=2020-09-16, status=1, ipAttribution=)]
    2020-09-16 肿肿

    机制研究离临床仍然有距离,不过与临床结合思考,仍然有帮助的,不能仅仅是纯临床思维,转化思维同样重要

    0

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    2020-09-16 rayms

    厉害,越来越好

    0

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