Drosophila Strip serves as a platform for early endosome organization during axon elongation.

Drosophila Strip serves as a platform for early endosome organization during axon elongation.
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果蝇条是在轴突伸长期间的早期内体组织的平台。

DOI:
10.1038/ncomms6180
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发表时间:
2014-10-14
影响因子:
16.6
通讯作者:
Chihara, Takahiro
Chihara, Takahiro
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Sakuma, Chisako;Kawauchi, Takeshi;Haraguchi, Shuka;Shikanai, Mima;Yamaguchi, Yoshifumi;Gelfand, Vladimir I.;Luo, Liqun;Miura, Masayuki;Chihara, Takahiro

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在神经元形态发生过程中,早期核内体对调节细胞信号传导和控制细胞表面分子的数量至关重要。早期核内体在同型融合前经历逆行运输(聚集)。已知小GTPase Rab5促进早期内体融合,但将运输/聚集与Rab5活性联系起来的机制尚不清楚。在这里,我们发现果蝇条带是神经元形态发生的关键调节因子。条带敲除干扰早期核内体聚集,rab5阳性早期核内体变小、分散。Strip与glue(动力蛋白依赖性运输的调节因子)和Sprint (Rab5的鸟嘌呤核苷酸交换因子)在遗传和生化上相互作用,表明Strip是逆行运输和Rab5激活之间的分子连接体。条带突变神经元中Rab5活性形式的过表达可抑制轴突伸长缺陷。因此,条带作为早期核内体组织的分子平台,在神经元形态发生中起着重要作用。
Early endosomes are essential for regulating cell signalling and controlling the amount of cell surface molecules during neuronal morphogenesis. Early endosomes undergo retrograde transport (clustering) before their homotypic fusion. Small GTPase Rab5 is known to promote early endosomal fusion, but the mechanism linking the transport/clustering with Rab5 activity is unclear. Here we show that Drosophila Strip is a key regulator for neuronal morphogenesis. strip knockdown disturbs the early endosome clustering and Rab5-positive early endosomes become smaller and scattered. Strip genetically and biochemically interacts with both Glued (the regulator of dynein-dependent transport) and Sprint (the guanine nucleotide exchange factor for Rab5), suggesting that Strip is a molecular linker between retrograde transport and Rab5 activation. Overexpression of an active form of Rab5 in strip mutant neurons suppresses the axon elongation defects. Thus, Strip acts as a molecular platform for the early endosome organization that plays important roles in neuronal morphogenesis.
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