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  • Title: Chloride channel 4 is required for nerve growth factor-induced TrkA signaling and neurite outgrowth in PC12 cells and cortical neurons.
    Author: Hur J, Jeong HJ, Park J, Jeon S.
    Journal: Neuroscience; 2013 Dec 03; 253():389-97. PubMed ID: 24036377.
    Abstract:
    We have previously shown that chloride ion flux plays an important role in receptor tyrosine kinase A (TrkA)-mediated signaling pathway during nerve growth factor (NGF)-induced differentiation in pheochromocytoma (PC12) cells. Here we found out that chloride channel 4 (CLC-4) is responsible for the NGF-induced neurite outgrowth in neuronal cells. Using a patch-clamp technique, we found that NGF treatment increased anionic conductance in PC12 cells, an effect which was blocked by transfection of siRNA of CLC-4. Also, the NGF-induced TrkA phosphorylation and subsequent Akt/moesin phosphorylation was suppressed in the CLC-4 knock down cells. Moreover, CLC-4 knock down also suppressed the neurite outgrowth in response to long-term treatment of NGF in PC12 cells and in primary cortical neurons. In summary, our results suggest that CLC-4 is an important mediator of the TrkA-mediated signaling pathway and thus, the NGF-induced differentiation of neuronal cells.
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