Hsp90 activity is necessary to acquire a proper neuronal polarization

被引:20
作者
Benitez, M. J. [1 ,4 ]
Sanchez-Ponce, D. [3 ]
Garrido, J. J. [2 ,3 ]
Wandosell, F. [1 ,2 ]
机构
[1] Univ Autonoma Madrid, CSIC UAM, Ctr Biol Mol Severo Ochoa, E-28049 Madrid, Spain
[2] Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain
[3] CSIC, Inst Cajal, Dept Mol Cellular & Dev Neurobiol, E-28002 Madrid, Spain
[4] Univ Autonoma Madrid, Dept Quim Fis Aplicada, E-28049 Madrid, Spain
来源
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH | 2014年 / 1843卷 / 02期
关键词
Neuronal chaperons; Hsp90; Axon; Neuronal polarity; PI3K-Akt pathway; HEAT-SHOCK PROTEINS; MOLECULAR CHAPERONE; NEURITE OUTGROWTH; GENE-EXPRESSION; AXON FORMATION; POLARITY; DIFFERENTIATION; ESTABLISHMENT; GSK-3-BETA; 17-ALLYLAMINO-17-DEMETHOXYGELDANAMYCIN;
D O I
10.1016/j.bbamcr.2013.11.013
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Chaperones are critical for the folding and regulation of a wide array of cellular proteins. Heat Shock Proteins (Hsps) are the most representative group of chaperones. Hsp90 represents up to 1-2% of soluble protein. Although the Hsp90 role is being studied in neurodegenerative diseases, its role in neuronal differentiation remains mostly unknown. Since neuronal polarity mechanisms depend on local stability and degradation, we asked whether Hsp90 could be a regulator of axonal polarity and growth. Thus, we studied the role of Hsp90 activity in a well established model of cultured hippocampal neurons using an Hsp90 specific inhibitor, 17-AAG. Our present data shows that Hsp90 inhibition at different developmental stages disturbs neuronal polarity formation or axonal elongation. Hsp90 inhibition during the first 3 h in culture promotes multiple axon morphology, while this inhibition after 3 h slows down axonal elongation. Hsp90 inhibition was accompanied by decreased Akt and GSK3 expression, as well as, a reduced Akt activity. In parallel, we detected an alteration of kinesin-1 subcellular distribution. Moreover, these effects were seconded by changes in Hsp70/Hsc70 subcellular localization that seem to compensate the lack of Hsp90 activity. In conclusion, our data strongly suggests that Hsp90 activity is necessary to control the expression, activity or location of specific kinases and motor proteins during the axon specification and axon elongation processes. Even more, our data demonstrate the existence of a "time-window" for axon specification in this model of cultured neurons after which the inhibition of Hsp90 only affects axonal elongation mechanisms. (C) 2013 Elsevier B.V. All rights reserved.
引用
收藏
页码:245 / 252
页数:8
相关论文
共 42 条
  • [41] GSK-3β regulates phosphorylation of CRMP-2 and neuronal polarity
    Yoshimura, T
    Kawano, Y
    Arimura, N
    Kawabata, S
    Kikuchi, A
    Kaibuchi, K
    [J]. CELL, 2005, 120 (01) : 137 - 149
  • [42] Repression of heat shock transcription factor HSF1 activation by HSP90 (HSP90 complex) that forms a stress-sensitive complex with HSF1
    Zou, JY
    Guo, YL
    Guettouche, T
    Smith, DF
    Voellmy, R
    [J]. CELL, 1998, 94 (04) : 471 - 480