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X 连锁凋亡抑制蛋白通过与 cRAF 和 Trk 相互作用负调控神经元分化。

X-linked inhibitor of apoptosis protein negatively regulates neuronal differentiation through interaction with cRAF and Trk.

机构信息

Institut de Neurociències and Dpt. Bioquímica and Biología Molecular, Universitat Autònoma de Barcelona, 08193 Cerdanyola del Vallès, Spain.

出版信息

Sci Rep. 2013;3:2397. doi: 10.1038/srep02397.

DOI:10.1038/srep02397
PMID:23928917
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3739015/
Abstract

X-linked Inhibitor of apoptosis protein (XIAP) has been classically identified as a cell death regulator. Here, we demonstrate a novel function of XIAP as a regulator of neurite outgrowth in neuronal cells. In PC12 cells, XIAP overexpression prevents NGF-induced neuronal differentiation, whereas NGF treatment induces a reduction of endogenous XIAP levels concomitant with the induction of neuronal differentiation. Accordingly, downregulation of endogenous XIAP protein levels strongly increases neurite outgrowth in PC12 cells as well as axonal and dendritic length in primary cortical neurons. The effects of XIAP are mediated by the mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinases (ERKs) pathway since blocking this pathway completely prevents the neuritogenesis mediated by XIAP downregulation. In addition, we found that XIAP binds to cRaf and Trk receptors. Our results demonstrate that XIAP plays a new role as a negative regulator of neurotrophin-induced neurite outgrowth and neuronal differentiation in developing neurons.

摘要

X 连锁凋亡抑制蛋白（XIAP）已被经典地鉴定为细胞死亡调节剂。在这里，我们证明了 XIAP 的一个新功能，作为神经元细胞中突起生长的调节剂。在 PC12 细胞中，XIAP 的过表达阻止了 NGF 诱导的神经元分化，而 NGF 处理诱导内源性 XIAP 水平的降低，伴随着神经元分化的诱导。因此，下调内源性 XIAP 蛋白水平强烈增加 PC12 细胞中的突起生长，以及原代皮质神经元中的轴突和树突长度。XIAP 的作用是通过丝裂原活化蛋白激酶（MEK）/细胞外信号调节激酶（ERK）途径介导的，因为阻断该途径完全阻止了 XIAP 下调介导的突起生成。此外，我们发现 XIAP 与 cRaf 和 Trk 受体结合。我们的结果表明，XIAP 在发育中的神经元中作为神经营养因子诱导的突起生长和神经元分化的负调节剂发挥新的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/865d/3739015/729ecfcdd8c1/srep02397-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/865d/3739015/307e6a96524b/srep02397-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/865d/3739015/1414dcb7d07c/srep02397-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/865d/3739015/80dc447ec21e/srep02397-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/865d/3739015/12f3b2f548ee/srep02397-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/865d/3739015/a0914940a1f0/srep02397-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/865d/3739015/c629fab3464f/srep02397-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/865d/3739015/729ecfcdd8c1/srep02397-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/865d/3739015/307e6a96524b/srep02397-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/865d/3739015/1414dcb7d07c/srep02397-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/865d/3739015/80dc447ec21e/srep02397-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/865d/3739015/12f3b2f548ee/srep02397-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/865d/3739015/a0914940a1f0/srep02397-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/865d/3739015/c629fab3464f/srep02397-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/865d/3739015/729ecfcdd8c1/srep02397-f7.jpg

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