Heat Shock Protein 90 is Required for cAMP-Induced Differentiation in Rat Primary Schwann Cells
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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.
KeywordscAMP SC differentiation ErbB2 Gab1 Hsp90
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).
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Conflict of interest
The authors have no potential conflicts of interest to disclose.
- 12.Ghidinelli M, Poitelon Y, Shin YK, Ameroso D, Williamson C, Ferri C, Pellegatta M, Espino K, Mogha A, Monk K, Podini P, Taveggia C, Nave KA, Wrabetz L, Park HT, Feltri ML (2017) Laminin 211 inhibits protein kinase A in Schwann cells to modulate neuregulin 1 type III-driven myelination. PLoS Biol 15:e2001408CrossRefGoogle Scholar
- 30.Grenert JP, Sullivan WP, Fadden P, Haystead TA, Clark J, Mimnaugh E, Krutzsch H, Ochel HJ, Schulte TW, Sausville E, Neckers LM, Toft DO (1997) The amino-terminal domain of heat shock protein 90 (hsp90) that binds geladanamycin is an ATP-ADP swich domain that regulates hsp90 conformation. J Biol Chem 272:23843–23850CrossRefGoogle Scholar
- 39.Osawa M, Itoh S, Ohta S, Huang Q, Berk BC, Mamarosh NL, Che W, Ding B, Yan C, Abe J (2004) ERK1/2 associates with the c-Met-binding domain of growth factor receptor-bound protein 1 (Grb2)-associated binder-1 (Gab1): role in ERK1/2 and early growth response factor-1 (Egr-1) nuclear accumulation. J Biol Chem 279:29691–29699CrossRefGoogle Scholar