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 J CELL BIOL ：遗传发育所揭示神经发育必需因子及其作用机制

2017-10-26 佚名 遗传发育所

遗传发育神经发育必需因子作用机制
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近日，中国科学院遗传与发育生物学研究所杨崇林研究组和郭伟翔研究组的联合研究论文，发表在The Journal of Cell Biology上。论文揭示了一个新的神经发育的关键蛋白-WDR91，并阐明了其作为小GTP酶Rab7效应因子在溶酶体运输通路中发挥重要作用。

近日，中国科学院遗传与发育生物学研究所杨崇林研究组和郭伟翔研究组的联合研究论文，发表在The Journal of Cell Biology上。论文揭示了一个新的神经发育的关键蛋白-WDR91，并阐明了其作为小GTP酶Rab7效应因子在溶酶体运输通路中发挥重要作用。

内吞体-溶酶体运输调控细胞内信号转导、细胞膜修复、细胞迁移和神经轴突生长等过程，对于维持细胞稳态和发育至关重要。其中，早-晚期内吞体的转换是内吞体-溶酶体运输的关键环节。早-晚期内吞体的转换需要将早期内吞体上的特征性小GTP酶Rab5和磷脂酰肌-3磷酸(PtdIns3P)转换为晚期内吞体上的特征性小GTP酶Rab7和磷脂酰肌-3，5二磷酸((PtdIns(3，5)P2)。杨崇林研究组的前期研究发现了线虫中的两个蛋白SORF-1和SORF-2，它们相互作用并与内吞体上磷脂酰肌-3磷酸激酶(PI3K)复合体互作，从而抑制PtdIns3P的合成，促进早-晚期内吞体转化。SORF-1和SORF-2的人类同源蛋白WDR91和WDR81以同样机制发挥作用。

杨崇林研究组和郭伟翔研究组合作发现，WDR91通过其C-端与活化形式的小GTP酶Rab7结合，从而被招募到内吞体上。同时，WDR91通过其N-端与PI3K复合体的Beclin1亚基相结合。WDR91因而特异地在内吞体上抑制PI3K复合物的活性，使内吞体转换所需要的Rab5-Rab7转换与PtdIns3P-PtdIns(3，5)P2转换同步进行。Wdr91敲除小鼠在出生后几个小时内死亡。在脑组织中特异性敲除Wdr91后，小鼠表现为大脑发育异常，在出生3至4周后死亡。在缺失Wdr91的原代神经元中，有大量异常增大的内吞体存在，神经元树突的长度和复杂度均显着降低。这些内吞体缺陷和神经发育缺陷可被野生型WDR91蛋白恢复，但却不能被与Rab7结合的有缺陷的WDR91突变蛋白恢复。研究表明，WDR91是Rab7的一个新的效应因子，在对神经元的发育中发挥不可或缺的作用。

研究工作受到国家重点基础研究发展计划、国家自然科学基金委、中科院跨学科创新团队、中科院前沿科学研究重点项目的资助。

A.WDR91与活性形式GTP-rab7的相互作用。B.WDR91被野生型Rab7或持续活化的GTP-Rab7(Q67L)招募到内吞体上。C.脑组织特异性敲除Wdr91小鼠的大脑发育异常。D.野生型WDR91而非Rab7结合缺陷性的WDR91突变体使缺失Wdr91的异常原代神经元恢复为正常。

原始出处：
Liu K, Xing R, Jian Y, et al.WDR91 is a Rab7 effector required for neuronal development.J Cell Biol. 2017 Oct 2;216(10):3307-3321. doi: 10.1083/jcb.201705151. Epub 2017 Aug 31.

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    2018-07-23 维他命

    #CEL#

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    2018-06-03 12498ebem31暂无昵称

    #Biol#

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    2018-04-08 zhaozhouchifen

    #Cell#

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    2018-08-14 sunylz

    #Bio#

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    2017-10-28 12499e01m47暂无昵称

    #神经发育#

    0

  6. [GetPortalCommentsPageByObjectIdResponse(id=1960505, encodeId=615c196050587, content=<a href='/topic/show?id=dbe6445416' target=_blank style='color:#2F92EE;'>#CEL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=23, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4454, encryptionId=dbe6445416, topicName=CEL)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c3ff68, createdName=维他命, createdTime=Mon Jul 23 06:14:00 CST 2018, time=2018-07-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1767289, encodeId=a5891e672893a, content=<a href='/topic/show?id=64f5343e2f' target=_blank style='color:#2F92EE;'>#Biol#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3437, encryptionId=64f5343e2f, topicName=Biol)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=446937890434, createdName=12498ebem31暂无昵称, createdTime=Sun Jun 03 04:14:00 CST 2018, time=2018-06-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1870243, encodeId=34a118e0243ff, content=<a href='/topic/show?id=fd764459a8' target=_blank style='color:#2F92EE;'>#Cell#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=24, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4459, encryptionId=fd764459a8, topicName=Cell)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=524d95, createdName=zhaozhouchifen, createdTime=Sun Apr 08 15:14:00 CST 2018, time=2018-04-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1917742, encodeId=208f191e74288, content=<a href='/topic/show?id=4f26341994' target=_blank style='color:#2F92EE;'>#Bio#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3419, encryptionId=4f26341994, topicName=Bio)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=12de429, createdName=sunylz, createdTime=Tue Aug 14 12:14:00 CST 2018, time=2018-08-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1345608, encodeId=811e13456084f, content=<a href='/topic/show?id=37c9e4238b9' target=_blank style='color:#2F92EE;'>#神经发育#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=74238, encryptionId=37c9e4238b9, topicName=神经发育)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d7532500500, createdName=12499e01m47暂无昵称, createdTime=Sat Oct 28 06:14:00 CST 2017, time=2017-10-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1347231, encodeId=40e3134e2313e, content=<a href='/topic/show?id=88713e938c1' target=_blank style='color:#2F92EE;'>#发育#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=37938, encryptionId=88713e938c1, topicName=发育)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=f4c124, createdName=neurowu, createdTime=Sat Oct 28 06:14:00 CST 2017, time=2017-10-28, status=1, ipAttribution=)]
    2017-10-28 neurowu

    #发育#

    0