Sprouty2 down-regulation promotes axon growth by adult sensory neurons

被引：37

作者：

Hausott, Barbara ^{[1
]}

Vallant, Natalie ^{[1
]}

Auer, Maria ^{[1
]}

Yang, Lin ^{[1
,3
]}

Dai, Fangping ^{[2
]}

Brand-Saberi, Beate ^{[2
,4
]}

Klimaschewski, Lars ^{[1
]}

机构：

[1] Innsbruck Med Univ, Div Neuroanat, A-6020 Innsbruck, Austria

[2] Univ Freiburg, Inst Anat & Cell Biol 2, D-79104 Freiburg, Germany

[3] Capital Med Univ, Div Anat & Embryol, Beijing 100069, Peoples R China

[4] Ruhr Univ Bochum, Inst Anat, D-44801 Bochum, Germany

来源：

MOLECULAR AND CELLULAR NEUROSCIENCE | 2009年 / 42卷 / 04期

基金：

奥地利科学基金会;

关键词：

CENTRAL-NERVOUS-SYSTEM; TYROSINE KINASE; ERK ACTIVATION; MAP KINASE; PC12; CELLS; IN-VIVO; DIFFERENTIATION; PROTEINS; RAF; SURVIVAL;

D O I：

10.1016/j.mcn.2009.08.005

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Fibroblast growth factors (FGFs) play a prominent role in axonal growth during development and repair. Treatment with FGF-2 or overexpression of FGF receptors promotes peripheral axon regeneration mainly by activation of extracellular signal-regulated kinase (ERK). The Ras/Raf/ERK pathway is under the control of Sprouty proteins acting as negative feedback inhibitors. We investigated the expression of Sprouty isoforms in adult sensory neurons of dorsal root ganglia (DRG) as well as the effects of Sprouty inhibition on axon growth by small interfering RNAs (siRNAs). Sprouty2 revealed the highest expression level in DRG neurons. Down-regulation of Sprouty2 promoted elongative axon growth by adult sensory neurons accompanied by enhanced FGF-2-induced activation of ERK and Ras, whereas Sprouty2 overexpression inhibited axon growth. Sprouty2 was not regulated in vivo in response to a sciatic nerve lesion. Together, our results imply that Sprouty2 is highly expressed in adult peripheral neurons and its down-regulation strongly promotes elongative axon growth by activation of the Ras/Raf/ERK pathway. (C) 2009 Elsevier Inc. All rights reserved.

引用

页码：328 / 340

页数：13

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