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Nature Cell Biology：O-GlcNAc糖基化修饰SNAP-29调控自噬小体的成熟

2014-11-30 佚名 生物谷

自噬小体
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中科院生物物理所张宏研究组最近在Nature Cell Biology杂志上发表题为O-GlcNAc-modification of ?SNAP-29 regulates autophagosome maturation的文章介绍了他们关于O-GlcNAc糖基化修饰SNAP-29并调控自噬小体的成熟的研究成果。这项研究工作首次报道了细胞自噬小体的成熟可以被营养状态感应因子OGT介导的SNAP-29

中科院生物物理所张宏研究组最近在Nature Cell Biology杂志上发表题为O-GlcNAc-modification of ?SNAP-29 regulates autophagosome maturation的文章介绍了他们关于O-GlcNAc糖基化修饰SNAP-29并调控自噬小体的成熟的研究成果。这项研究工作首次报道了细胞自噬小体的成熟可以被营养状态感应因子OGT介导的SNAP-29的O-GlcNAc糖基化修饰所调节。这是继mTORC 和VPS34 复合体外，第三个能够感应细胞的营养状态从而调控自噬活性的节点。

细胞自噬是重要的胞内降解过程，在细胞的生命活动中起到重要作用。在饥饿状态及其他应激条件下，细胞自噬被激活，胞内组分被自噬小体运输到溶酶体进行降解，从而提供特殊环境下细胞生存所需要的营养和能量。细胞自噬的调控大致可以分为三个水平：①自噬起始的调控。多种信号转导通路参与调节自噬的起始，如AMPK信号通路、mTOR信号通路、Ras/PKA信号通路等等；②自噬小体形成的调控。细胞自噬小体形成过程中，ClassIII PI3K-BECLIN1复合体发挥重要作用。③细胞自噬小体成熟的调控。双层膜结构的自噬小体形成之后，需要通过内含体和溶酶体融合，最终形成自噬溶酶体从而将底物降解。该过程称为自噬小体的成熟。但是到目前为止，关于自噬小体成熟的调控机制知之甚少。

张宏等人研究发现了一个多细胞生物特异的细胞自噬基因epg-5/EPG5。在epg-5突变体中，细胞自噬结构大量累积。通过epg-5突变体的抑制子筛选，科学家获得可能参与调节自噬小体成熟的相关基因。其中有一个bp815的突变体是ogt-1的一个等位基因，该基因负责编码哺乳动物细胞O-GlcNAc转移酶OGT的同源物。研究人员随后证实线虫ogt-1的突变可以提高细胞自噬活性，从而促进蛋白聚集体的降解。哺乳动物细胞中，OGT敲减后可以显着促进细胞自噬降解过程。OGT功能缺失可以促进细胞自噬小体和内含体以及溶酶体的融合过程。进一步的体内和体外实验研究发现，参与细胞自噬小体成熟的SNAREs复合体组分之一的SNAP-29可以被OGT介导的O-GlcNAc糖基化修饰。O-GlcNAc修饰的SNAP-29可以抑制其与STX17以及VAMP8形成SNAREs功能复合体。在OGT敲减细胞中，SNAP-29的糖基化修饰水平显着降低，从而促进了STX17-SNAP-29-VAMP8复合体的形成，最终促进了细胞自噬小体的成熟。质谱分析和定点突变实验鉴定了SNAP-29中有四个氨基酸可以被OGT介导的O-GlcNAc糖基化修饰。过表达糖基化修饰位点突变的SNAP-29可以显着促进细胞自噬降解活性。同时，研究表明线虫SNAP-29也能够被O-GlcNAc糖基化修饰。在饥饿的线虫中，GlcNAc供体UDP-GlcNAc的水平显着下降，SNAP-29的O-GlcNAcylation修饰水平明显降低。

原始出处

Guo B1, Liang Q1, Li L2, Hu Z3, Wu F1, Zhang P1, Ma Y2, Zhao B3, Kovács AL4, Zhang Z2, Feng D3, Chen S2, Zhang H1.O-GlcNAc-modification of SNAP-29 regulates autophagosome maturation.Nat Cell Biol. 2014 Nov 24.

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    2015-04-08 zhaozhouchifen

    #Cell#

    0

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    2015-10-30 智者为医08

    #Nat#

    0

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    2015-05-22 liuquan

    #糖基化修饰#

    0

  4. [GetPortalCommentsPageByObjectIdResponse(id=1868959, encodeId=5093186895986, content=<a href='/topic/show?id=fd764459a8' target=_blank style='color:#2F92EE;'>#Cell#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4459, encryptionId=fd764459a8, topicName=Cell)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=524d95, createdName=zhaozhouchifen, createdTime=Wed Apr 08 01:30:00 CST 2015, time=2015-04-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1880396, encodeId=0e361880396d4, content=<a href='/topic/show?id=3b2112532d8' target=_blank style='color:#2F92EE;'>#Nat#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=21, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12532, encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4dfa37, createdName=智者为医08, createdTime=Fri Oct 30 09:30:00 CST 2015, time=2015-10-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2085428, encodeId=80772085428a2, content=<a href='/topic/show?id=69cde66454a' target=_blank style='color:#2F92EE;'>#糖基化修饰#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=24, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=76645, encryptionId=69cde66454a, topicName=糖基化修饰)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=28b7142, createdName=liuquan, createdTime=Fri May 22 23:30:00 CST 2015, time=2015-05-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1766914, encodeId=19501e6691432, content=<a href='/topic/show?id=64f5343e2f' target=_blank style='color:#2F92EE;'>#Biol#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=19, 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 Aug 02 15:30:00 CST 2015, time=2015-08-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1917099, encodeId=0a3f191e099e9, content=<a href='/topic/show?id=4f26341994' target=_blank style='color:#2F92EE;'>#Bio#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=21, 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 Mar 31 12:30:00 CST 2015, time=2015-03-31, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1959207, encodeId=ecb8195920e7e, content=<a href='/topic/show?id=dbe6445416' target=_blank style='color:#2F92EE;'>#CEL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=21, 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 Jun 22 06:30:00 CST 2015, time=2015-06-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1318282, encodeId=b4101318282d2, content=<a href='/topic/show?id=b5dde6644b1' target=_blank style='color:#2F92EE;'>#糖基化#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=22, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=76644, encryptionId=b5dde6644b1, topicName=糖基化)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=43cb463, createdName=lfyang, createdTime=Tue Dec 02 03:30:00 CST 2014, time=2014-12-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1569261, encodeId=ca4e156926131, content=<a href='/topic/show?id=1c562e42646' target=_blank style='color:#2F92EE;'>#修饰#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=20, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=27426, encryptionId=1c562e42646, topicName=修饰)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=29c615505859, createdName=zhangyxzsh, createdTime=Tue Dec 02 03:30:00 CST 2014, time=2014-12-02, status=1, ipAttribution=)]
    2015-08-02 12498ebem31暂无昵称

    #Biol#

    0

  5. [GetPortalCommentsPageByObjectIdResponse(id=1868959, encodeId=5093186895986, content=<a href='/topic/show?id=fd764459a8' target=_blank style='color:#2F92EE;'>#Cell#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4459, encryptionId=fd764459a8, topicName=Cell)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=524d95, createdName=zhaozhouchifen, createdTime=Wed Apr 08 01:30:00 CST 2015, time=2015-04-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1880396, encodeId=0e361880396d4, content=<a href='/topic/show?id=3b2112532d8' target=_blank style='color:#2F92EE;'>#Nat#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=21, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12532, encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4dfa37, createdName=智者为医08, createdTime=Fri Oct 30 09:30:00 CST 2015, time=2015-10-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2085428, encodeId=80772085428a2, content=<a href='/topic/show?id=69cde66454a' target=_blank style='color:#2F92EE;'>#糖基化修饰#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=24, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=76645, encryptionId=69cde66454a, topicName=糖基化修饰)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=28b7142, createdName=liuquan, createdTime=Fri May 22 23:30:00 CST 2015, time=2015-05-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1766914, encodeId=19501e6691432, content=<a href='/topic/show?id=64f5343e2f' target=_blank style='color:#2F92EE;'>#Biol#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=19, 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 Aug 02 15:30:00 CST 2015, time=2015-08-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1917099, encodeId=0a3f191e099e9, content=<a href='/topic/show?id=4f26341994' target=_blank style='color:#2F92EE;'>#Bio#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=21, 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 Mar 31 12:30:00 CST 2015, time=2015-03-31, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1959207, encodeId=ecb8195920e7e, content=<a href='/topic/show?id=dbe6445416' target=_blank style='color:#2F92EE;'>#CEL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=21, 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 Jun 22 06:30:00 CST 2015, time=2015-06-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1318282, encodeId=b4101318282d2, content=<a href='/topic/show?id=b5dde6644b1' target=_blank style='color:#2F92EE;'>#糖基化#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=22, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=76644, encryptionId=b5dde6644b1, topicName=糖基化)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=43cb463, createdName=lfyang, createdTime=Tue Dec 02 03:30:00 CST 2014, time=2014-12-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1569261, encodeId=ca4e156926131, content=<a href='/topic/show?id=1c562e42646' target=_blank style='color:#2F92EE;'>#修饰#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=20, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=27426, encryptionId=1c562e42646, topicName=修饰)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=29c615505859, createdName=zhangyxzsh, createdTime=Tue Dec 02 03:30:00 CST 2014, time=2014-12-02, status=1, ipAttribution=)]
    2015-03-31 sunylz

    #Bio#

    0

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    2015-06-22 维他命

    #CEL#

    0

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    2014-12-02 lfyang

    #糖基化#

    0

  8. [GetPortalCommentsPageByObjectIdResponse(id=1868959, encodeId=5093186895986, content=<a href='/topic/show?id=fd764459a8' target=_blank style='color:#2F92EE;'>#Cell#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4459, encryptionId=fd764459a8, topicName=Cell)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=524d95, createdName=zhaozhouchifen, createdTime=Wed Apr 08 01:30:00 CST 2015, time=2015-04-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1880396, encodeId=0e361880396d4, content=<a href='/topic/show?id=3b2112532d8' target=_blank style='color:#2F92EE;'>#Nat#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=21, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12532, encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4dfa37, createdName=智者为医08, createdTime=Fri Oct 30 09:30:00 CST 2015, time=2015-10-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2085428, encodeId=80772085428a2, content=<a href='/topic/show?id=69cde66454a' target=_blank style='color:#2F92EE;'>#糖基化修饰#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=24, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=76645, encryptionId=69cde66454a, topicName=糖基化修饰)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=28b7142, createdName=liuquan, createdTime=Fri May 22 23:30:00 CST 2015, time=2015-05-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1766914, encodeId=19501e6691432, content=<a href='/topic/show?id=64f5343e2f' target=_blank style='color:#2F92EE;'>#Biol#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=19, 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 Aug 02 15:30:00 CST 2015, time=2015-08-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1917099, encodeId=0a3f191e099e9, content=<a href='/topic/show?id=4f26341994' target=_blank style='color:#2F92EE;'>#Bio#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=21, 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 Mar 31 12:30:00 CST 2015, time=2015-03-31, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1959207, encodeId=ecb8195920e7e, content=<a href='/topic/show?id=dbe6445416' target=_blank style='color:#2F92EE;'>#CEL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=21, 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 Jun 22 06:30:00 CST 2015, time=2015-06-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1318282, encodeId=b4101318282d2, content=<a href='/topic/show?id=b5dde6644b1' target=_blank style='color:#2F92EE;'>#糖基化#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=22, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=76644, encryptionId=b5dde6644b1, topicName=糖基化)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=43cb463, createdName=lfyang, createdTime=Tue Dec 02 03:30:00 CST 2014, time=2014-12-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1569261, encodeId=ca4e156926131, content=<a href='/topic/show?id=1c562e42646' target=_blank style='color:#2F92EE;'>#修饰#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=20, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=27426, encryptionId=1c562e42646, topicName=修饰)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=29c615505859, createdName=zhangyxzsh, createdTime=Tue Dec 02 03:30:00 CST 2014, time=2014-12-02, status=1, ipAttribution=)]
    2014-12-02 zhangyxzsh

    #修饰#

    0