التفاصيل البيبلوغرافية
| العنوان: |
Hsp90 activity is necessary to acquire a proper neuronal polarization |
| المؤلفون: |
Francisco Wandosell, Diana Sánchez-Ponce, María J. Benítez, Juan José Garrido |
| المصدر: |
Digital.CSIC. Repositorio Institucional del CSIC
instname |
| بيانات النشر: |
Elsevier BV, 2014. |
| سنة النشر: |
2014 |
| مصطلحات موضوعية: |
Lactams, Macrocyclic, Growth Cones, Regulator, Kinesins, Hsp90, Neuronal chaperons Hsp90 Axon Neuronal polarity PI3K Akt pathway, Biology, Hippocampus, Axon, Motor protein, Glycogen Synthase Kinase 3, Mice, PI3K–Akt pathway, Heat shock protein, Benzoquinones, polycyclic compounds, medicine, Animals, HSP70 Heat-Shock Proteins, HSP90 Heat-Shock Proteins, Phosphorylation, Protein kinase B, Molecular Biology, PI3K/AKT/mTOR pathway, Neurons, Neuronal polarity, Cell Polarity, Neuronal chaperons, Cell Biology, Axons, Hsp70, Cell biology, Protein Transport, medicine.anatomical_structure, nervous system, biology.protein, Proto-Oncogene Proteins c-akt, Subcellular Fractions |
| الوصف: |
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. © 2013 Elsevier B.V. |
| تدمد: |
0167-4889 |
| DOI: |
10.1016/j.bbamcr.2013.11.013 |
| URL الوصول: |
https://explore.openaire.eu/search/publication?articleId=doi_dedup___::48563c80a375079589ab67ca659ee55b |
| Rights: |
OPEN |
| رقم الانضمام: |
edsair.doi.dedup.....48563c80a375079589ab67ca659ee55b |
| قاعدة البيانات: |
OpenAIRE |