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J Cell Sci：遗传发育所揭示神经突触发育调控机制

2016-12-15 遗传与发育生物学研究所 遗传与发育生物学研究所

神经突触发育调控机制
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MacCer和C16:1脂肪酸平行调控NMJ生长发育脂质代谢对大脑发育与功能至关重要。脂酰辅酶A合成酶长链家族成员4 (ACSL4) 突变导致非综合征型X连锁智力低下 (Intellectual disability, ID)。果蝇ACSL3/4的同源基因dAcsl突变体表现明显过度生长的神经肌肉突触 (Neuromuscular junction, NMJ) ，表明dAcsl抑制NMJ生长。但是

MacCer和C16:1脂肪酸平行调控NMJ生长发育

脂质代谢对大脑发育与功能至关重要。脂酰辅酶A合成酶长链家族成员4 (ACSL4) 突变导致非综合征型X连锁智力低下 (Intellectual disability, ID)。果蝇ACSL3/4的同源基因dAcsl突变体表现明显过度生长的神经肌肉突触 (Neuromuscular junction, NMJ) ，表明dAcsl抑制NMJ生长。但是dAcsl如何通过调控脂代谢而影响大脑和NMJ突触发育的分子细胞机制目前还不清楚。

中国科学院遗传与发育生物学研究所张永清研究组长期致力于突触发育和功能调控及相关神经精神疾病发病机制的研究，与遗传发育所研究员税光厚领导的脂质组学平台合作发现在dAcsl突变体神经系统中三种脂筏(Lipid raft) 的重要成分甘露糖-葡萄糖神经酰胺 (Mannosyl glucosylceramide, MacCer)、磷酸乙醇胺神经酰胺 (Phosphoethanolamine ceramide, PE-Cer) 和麦角固醇(Ergosterol) 含量增高。Acsl突变体大脑中C16:1脂肪酸减少，恢复Acsl的表达能有效挽救NMJ的发育并上调BMP信号通路。在Acsl突变体的NMJ中MacCer 和sterol含量提高促进了NMJ突触的生长，但是并没有通过上调BMP信号通路。综上所述，研究发现Acsl通过刺激C16:1脂肪酸的产量并抑制脂筏相关脂质水平而抑制NMJ突触的生长发育。上述结果为理解ACSL4相关的ID发病机理提供了新的思路和防治靶点。

该研究结果于近日在线发表于《细胞科学杂志》（Journal of Cell Science，DOI:10.1242/jcs.195032），张永清研究组的博士后黄琰是该论文的第一作者。该研究工作得到了国家自然科学基金委、科技部和中科院的资助。

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    2017-10-28 维他命

    #CEL#

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    2017-04-24 zhaozhouchifen

    #Cell#

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    2016-12-25 zhanglin3087

    #神经突触#

    0

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    2016-12-17 neurowu

    #发育#

    0

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    2016-12-17 ms691033630344116

    #突触#

    0

  6. [GetPortalCommentsPageByObjectIdResponse(id=1959941, encodeId=b22a1959941a0, content=<a href='/topic/show?id=dbe6445416' target=_blank style='color:#2F92EE;'>#CEL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, 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=Sat Oct 28 01:29:00 CST 2017, time=2017-10-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1869682, encodeId=6fb71869682ec, content=<a href='/topic/show?id=fd764459a8' target=_blank style='color:#2F92EE;'>#Cell#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4459, encryptionId=fd764459a8, topicName=Cell)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=524d95, createdName=zhaozhouchifen, createdTime=Mon Apr 24 11:29:00 CST 2017, time=2017-04-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1651646, encodeId=73d016516464d, content=<a href='/topic/show?id=a8e8e4433c9' target=_blank style='color:#2F92EE;'>#神经突触#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=74433, encryptionId=a8e8e4433c9, topicName=神经突触)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=36fa24222131, createdName=zhanglin3087, createdTime=Sun Dec 25 00:29:00 CST 2016, time=2016-12-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1347131, encodeId=ee9e134e131b3, content=<a href='/topic/show?id=88713e938c1' target=_blank style='color:#2F92EE;'>#发育#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, 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 Dec 17 06:29:00 CST 2016, time=2016-12-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1478776, encodeId=24c914e8776e1, content=<a href='/topic/show?id=76efe555021' target=_blank style='color:#2F92EE;'>#突触#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=39, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=75550, encryptionId=76efe555021, topicName=突触)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c5207457717, createdName=ms691033630344116, createdTime=Sat Dec 17 06:29:00 CST 2016, time=2016-12-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1497609, encodeId=29de149e60956, content=<a href='/topic/show?id=02599201364' target=_blank style='color:#2F92EE;'>#调控机制#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=92013, encryptionId=02599201364, topicName=调控机制)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=2bce9348572, createdName=villahu, createdTime=Sat Dec 17 06:29:00 CST 2016, time=2016-12-17, status=1, ipAttribution=)]
    2016-12-17 villahu

    #调控机制#

    0

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