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Blood：Weibel-Palade小体的邻近蛋白质组学揭示VWF分泌的新调控因子

2019-07-04 MedSci MedSci原创

Weibel-Palade小体vWF蛋白质组学Munc13-2
关注

Weibel-Palade小体(WPB)是一种特殊的内皮细胞分泌细胞器，可储存调节血管止血和局部炎症的因子。内皮细胞活化触发WPB快速分泌，导致白细胞滚动和血小板捕获相关的粘附分子(分别是P-选择素和血管性血友病因子[VWF])呈现于细胞表面。虽然已知WPB是一种重要的分泌细胞器，但尚无对WPB有关因素的全面了解。

中心点：

体内Weibel-Palade小体靶向APEX2构造的蛋白质组学分析可揭示细胞器相关的蛋白质组。

Munc13-2是一种新的正性调控内皮细胞分泌血管性血友病因子的因子。

摘要：

Weibel-Palade小体(WPB)是一种特殊的内皮细胞分泌细胞器，可储存调节血管止血和局部炎症的因子。内皮细胞活化触发WPB快速分泌，导致白细胞滚动和血小板捕获相关的粘附分子(分别是P-选择素和血管性血友病因子[VWF])呈现于细胞表面。虽然已知WPB是一种重要的分泌细胞器，但尚无对WPB有关因素的全面了解。

Anna Holthenrich等人尝试通过使用过氧化物酶APEX2与两个已知的WPB相关蛋白(Rab GTPases Rab3b和Rab27a)结合的近距离蛋白质组学方法来解决上述问题。

结果发现APEX2- rab3b /27a融合构建物可正确靶向原位内皮细胞的WPB，而且WPB招募APEX2可使其邻近的蛋白发生生物素化。对泛素化的蛋白进行质谱分析鉴定出183个WPB相关的蛋白。虽然其中有部分是已报道的定位到WPB上的因子，但大部分都是既往未发现与WPB生物学相关的蛋白。其中SNARW互作蛋白Munc13-2可特异性的定位到WPB，是促进组胺诱发的WPB胞吐和VWF分泌的新因子。

总而言之，基于APEX2的邻近蛋白组学可用于特异性的识别原位内皮细胞中与新细胞器相关的因子。

原始出处：

Anna Holthenrich， et al.Proximity proteomics of endothelial Weibel-Palade bodies identifies novel regulator of von-Willebrand factor secretion. Blood 2019 ：blood.2019000786； doi： https：//doi.org/10.1182/blood.2019000786

本文系梅斯医学（MedSci）原创编译，转载需授权！

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    2020-01-04 ms55066533437992

    #ALA#

    0

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    2019-10-08 gwc392

    #分泌#

    0

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    2020-06-13 jjjiang0211

    #蛋白质组#

    0

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    2020-05-04 柳叶一刀

    #白质#

    0

  5. [GetPortalCommentsPageByObjectIdResponse(id=2077069, encodeId=aed620e70696e, content=<a href='/topic/show?id=955d226045' target=_blank style='color:#2F92EE;'>#ALA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=77, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=2260, encryptionId=955d226045, topicName=ALA)], attachment=null, authenticateStatus=null, createdAvatar=https://thirdwx.qlogo.cn/mmopen/vi_32/lGEyfsKnIkkH93xUPMrUUycLh2XOfJJsphwPsVqDx8somSOepIFy9QE0MVAwDW3AS7V1epJ4tbPL9ADJLicvm8A/132, createdBy=b5132500067, createdName=ms55066533437992, createdTime=Sat Jan 04 23:44:00 CST 2020, time=2020-01-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1682540, encodeId=84c41682540fa, content=<a href='/topic/show?id=d4d031e8074' target=_blank style='color:#2F92EE;'>#分泌#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=71, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=31780, encryptionId=d4d031e8074, topicName=分泌)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=0da227938338, createdName=gwc392, createdTime=Tue Oct 08 21:44:00 CST 2019, time=2019-10-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1754848, encodeId=10411e5484890, content=<a href='/topic/show?id=0a1688e33b3' target=_blank style='color:#2F92EE;'>#蛋白质组#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=89, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=88733, encryptionId=0a1688e33b3, topicName=蛋白质组)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=cf6736789983, createdName=jjjiang0211, createdTime=Sat Jun 13 05:44:00 CST 2020, time=2020-06-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1765784, encodeId=6b601e657843c, content=<a href='/topic/show?id=252ae1803a3' target=_blank style='color:#2F92EE;'>#白质#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=85, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=71803, encryptionId=252ae1803a3, topicName=白质)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=778d36, createdName=柳叶一刀, createdTime=Mon May 04 03:44:00 CST 2020, time=2020-05-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1297087, encodeId=1891129e08767, content=<a href='/topic/show?id=158288e017c' target=_blank style='color:#2F92EE;'>#蛋白质#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=66, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=88701, encryptionId=158288e017c, topicName=蛋白质)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c689267, createdName=cmj8wellington, createdTime=Sat Jul 06 11:44:00 CST 2019, time=2019-07-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1372597, encodeId=086e13e2597d5, content=<a href='/topic/show?id=afaa185637c' target=_blank style='color:#2F92EE;'>#vWF#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=79, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=18563, encryptionId=afaa185637c, topicName=vWF)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=5462342, createdName=sunmin0219, createdTime=Sat Jul 06 11:44:00 CST 2019, time=2019-07-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1631352, encodeId=0e5b16313520a, content=<a href='/topic/show?id=fe2c186546a' target=_blank style='color:#2F92EE;'>#Weibel-Palade小体#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=58, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=18654, encryptionId=fe2c186546a, topicName=Weibel-Palade小体)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4c37265, createdName=zhaojie88, createdTime=Sat Jul 06 11:44:00 CST 2019, time=2019-07-06, status=1, ipAttribution=)]
    2019-07-06 cmj8wellington

    #蛋白质#

    0

  6. [GetPortalCommentsPageByObjectIdResponse(id=2077069, encodeId=aed620e70696e, content=<a href='/topic/show?id=955d226045' target=_blank style='color:#2F92EE;'>#ALA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=77, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=2260, encryptionId=955d226045, topicName=ALA)], attachment=null, authenticateStatus=null, createdAvatar=https://thirdwx.qlogo.cn/mmopen/vi_32/lGEyfsKnIkkH93xUPMrUUycLh2XOfJJsphwPsVqDx8somSOepIFy9QE0MVAwDW3AS7V1epJ4tbPL9ADJLicvm8A/132, createdBy=b5132500067, createdName=ms55066533437992, createdTime=Sat Jan 04 23:44:00 CST 2020, time=2020-01-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1682540, encodeId=84c41682540fa, content=<a href='/topic/show?id=d4d031e8074' target=_blank style='color:#2F92EE;'>#分泌#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=71, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=31780, encryptionId=d4d031e8074, topicName=分泌)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=0da227938338, createdName=gwc392, createdTime=Tue Oct 08 21:44:00 CST 2019, time=2019-10-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1754848, encodeId=10411e5484890, content=<a href='/topic/show?id=0a1688e33b3' target=_blank style='color:#2F92EE;'>#蛋白质组#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=89, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=88733, encryptionId=0a1688e33b3, topicName=蛋白质组)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=cf6736789983, createdName=jjjiang0211, createdTime=Sat Jun 13 05:44:00 CST 2020, time=2020-06-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1765784, encodeId=6b601e657843c, content=<a href='/topic/show?id=252ae1803a3' target=_blank style='color:#2F92EE;'>#白质#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=85, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=71803, encryptionId=252ae1803a3, topicName=白质)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=778d36, createdName=柳叶一刀, createdTime=Mon May 04 03:44:00 CST 2020, time=2020-05-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1297087, encodeId=1891129e08767, content=<a href='/topic/show?id=158288e017c' target=_blank style='color:#2F92EE;'>#蛋白质#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=66, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=88701, encryptionId=158288e017c, topicName=蛋白质)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c689267, createdName=cmj8wellington, createdTime=Sat Jul 06 11:44:00 CST 2019, time=2019-07-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1372597, encodeId=086e13e2597d5, content=<a href='/topic/show?id=afaa185637c' target=_blank style='color:#2F92EE;'>#vWF#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=79, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=18563, encryptionId=afaa185637c, topicName=vWF)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=5462342, createdName=sunmin0219, createdTime=Sat Jul 06 11:44:00 CST 2019, time=2019-07-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1631352, encodeId=0e5b16313520a, content=<a href='/topic/show?id=fe2c186546a' target=_blank style='color:#2F92EE;'>#Weibel-Palade小体#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=58, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=18654, encryptionId=fe2c186546a, topicName=Weibel-Palade小体)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4c37265, createdName=zhaojie88, createdTime=Sat Jul 06 11:44:00 CST 2019, time=2019-07-06, status=1, ipAttribution=)]
    2019-07-06 sunmin0219

    #vWF#

    0

  7. [GetPortalCommentsPageByObjectIdResponse(id=2077069, encodeId=aed620e70696e, content=<a href='/topic/show?id=955d226045' target=_blank style='color:#2F92EE;'>#ALA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=77, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=2260, encryptionId=955d226045, topicName=ALA)], attachment=null, authenticateStatus=null, createdAvatar=https://thirdwx.qlogo.cn/mmopen/vi_32/lGEyfsKnIkkH93xUPMrUUycLh2XOfJJsphwPsVqDx8somSOepIFy9QE0MVAwDW3AS7V1epJ4tbPL9ADJLicvm8A/132, createdBy=b5132500067, createdName=ms55066533437992, createdTime=Sat Jan 04 23:44:00 CST 2020, time=2020-01-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1682540, encodeId=84c41682540fa, content=<a href='/topic/show?id=d4d031e8074' target=_blank style='color:#2F92EE;'>#分泌#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=71, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=31780, encryptionId=d4d031e8074, topicName=分泌)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=0da227938338, createdName=gwc392, createdTime=Tue Oct 08 21:44:00 CST 2019, time=2019-10-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1754848, encodeId=10411e5484890, content=<a href='/topic/show?id=0a1688e33b3' target=_blank style='color:#2F92EE;'>#蛋白质组#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=89, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=88733, encryptionId=0a1688e33b3, topicName=蛋白质组)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=cf6736789983, createdName=jjjiang0211, createdTime=Sat Jun 13 05:44:00 CST 2020, time=2020-06-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1765784, encodeId=6b601e657843c, content=<a href='/topic/show?id=252ae1803a3' target=_blank style='color:#2F92EE;'>#白质#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=85, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=71803, encryptionId=252ae1803a3, topicName=白质)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=778d36, createdName=柳叶一刀, createdTime=Mon May 04 03:44:00 CST 2020, time=2020-05-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1297087, encodeId=1891129e08767, content=<a href='/topic/show?id=158288e017c' target=_blank style='color:#2F92EE;'>#蛋白质#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=66, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=88701, encryptionId=158288e017c, topicName=蛋白质)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c689267, createdName=cmj8wellington, createdTime=Sat Jul 06 11:44:00 CST 2019, time=2019-07-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1372597, encodeId=086e13e2597d5, content=<a href='/topic/show?id=afaa185637c' target=_blank style='color:#2F92EE;'>#vWF#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=79, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=18563, encryptionId=afaa185637c, topicName=vWF)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=5462342, createdName=sunmin0219, createdTime=Sat Jul 06 11:44:00 CST 2019, time=2019-07-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1631352, encodeId=0e5b16313520a, content=<a href='/topic/show?id=fe2c186546a' target=_blank style='color:#2F92EE;'>#Weibel-Palade小体#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=58, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=18654, encryptionId=fe2c186546a, topicName=Weibel-Palade小体)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4c37265, createdName=zhaojie88, createdTime=Sat Jul 06 11:44:00 CST 2019, time=2019-07-06, status=1, ipAttribution=)]
    2019-07-06 zhaojie88

    #Weibel-Palade小体#

    0