GDNF isoform affects intracellular trafficking and secretion of GDNF in neuronal cells

GDNF isoform affects intracellular trafficking and secretion of GDNF in neuronal cells
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GDNF 异构体影响神经元细胞内 GDNF 的运输和分泌

DOI:
10.1016/j.brainres.2008.05.087
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发表时间:
2008-08-21
期刊:
影响因子:
2.9
通讯作者:
Chen, Zhe-Yu
Chen, Zhe-Yu
中科院分区:
医学3区
文献类型:
--
作者:
Wang, Yue;Geng, Zhao;Chen, Zhe-Yu

文献摘要

被引文献

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胶质细胞源性神经营养因子(Glial cell line derived neurotrophic factor,GDNF)在中枢和外周神经元的存活和功能中起重要作用,在人类和啮齿类动物中,GDNF以选择性剪接异构体(GDNF Delta 78)存在,其编码序列的前区有78 bp的缺失。GDNF亚型是否影响GDNF功能尚不清楚。在这里,我们研究了GDNF Delta 78亚型的分泌和细胞内定位。在神经元细胞群中。我们的数据表明,GDNF Delta 78的分泌减少和异常的细胞内分布发生在神经元细胞中。共定位研究揭示了GDNF Delta 78与高尔基体标记-TGN 38的更多定位,这表明GDNF Delta 78在高尔基体中的积累可能部分地解释了其细胞内运输和分泌缺陷。据我们所知,首次报道GDNF Delta 78同种型在GDNF细胞内运输和分泌方面存在缺陷。(C)2008 Elsevier B. V.保留所有权利。
Glial cell line derived neurotrophic factor (GDNF) plays a critical role in central and peripheral neuron survival and function, in human and rodents, GDNF exists in an alternative spliced isoform, (GDNF Delta 78), which has a 78 bp deletion in the pro-region of the GDNF encoding sequence. Whether the GDNF isoform affects GDNF function is unknown. Here, we investigated the secretion and intracellular localization of the GDNF Delta 78 isoform. in neuronal cell populations. Our data indicate that a decreased secretion and an abnormal intracellular distribution of GDNF Delta 78 occurred in neuronal cells. The colocalization studies revealed much more localization of GDNF Delta 78 with Golgi marker-TGN38, which indicates that the accumulation of GDNF Delta 78 in the Golgi apparatus might in part account for its intracellular trafficking and secretion deficit. To our knowledge, it is reported for the first time that the GDNF Delta 78 isoform has a deficit in GDNF intracellular trafficking and secretion. (C) 2008 Elsevier B.V. All rights reserved.