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Heat Shock Protein 90 is Required for cAMP-Induced Differentiation in Rat Primary Schwann Cells

  • Sang-Heum Han
  • Seong-Hoon Yun
  • Yoon-Kyoung Shin
  • Hwan-Tae ParkEmail author
  • Joo-In ParkEmail author
Original Paper
  • 29 Downloads

Abstract

Schwann cells (SCs) play an important role in producing myelin for rapid neurotransmission in the peripheral nervous system. Activation of the differentiation and myelination processes in SCs requires the expression of a series of transcriptional factors including Sox10, Oct6/Pou3f1, and Egr2/Krox20. However, functional interactions among several transcription factors are poorly defined and the important components of the regulatory network are still unknown. Until now, available evidence suggests that SCs require cAMP signaling to initiate the myelination program. Heat shock protein 90 (Hsp90) is known as a chaperone required to stabilize ErbB2 receptor. In recent years, it was reported that cAMP transactivated the ErbB2/ErbB3 signaling in SCs. However, the relationship between Hsp90 and cAMP-induced differentiation in SCs is undefined. Here we investigated the role of Hsp90 during cAMP-induced differentiation of SCs using Hsp90 inhibitor, geldanamycin and Hsp90 siRNA transfection. Our results showed that dibutyryl-cAMP (db-cAMP) treatment upregulated Hsp90 expression and led to nuclear translocation of Gab1/ERK, the downstream signaling pathway of the ErbB2 signaling mechanism in myelination. The expression of myelin-related genes and nuclear translocation of Gab1/ERK following db-cAMP treatment was inhibited by geldanamycin pretreatment and Hsp90 knockdown. These findings suggest that Hsp90 might play a role in cAMP-induced differentiation via stabilization of ErbB2 and nuclear translocation of Gab1/ERK in SCs.

Keywords

cAMP SC differentiation ErbB2 Gab1 Hsp90 

Notes

Acknowledgements

This work was supported by the National Research Foundation of Korea (NRF) funded by the Korean Government (MSIP) (No. 2016R1A5A2007009); and by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT and Future Planning (NRF-2017R1A2B4011428).

Compliance with Ethical Standards

Conflict of interest

The authors have no potential conflicts of interest to disclose.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of BiochemistryDong-A University College of MedicineBusanRepublic of Korea
  2. 2.Peripheral Neuropathy Research CenterDong-A UniversityBusanRepublic of Korea
  3. 3.Department of Molecular NeuroscienceDong-A University College of MedicineBusanRepublic of Korea

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