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Nerve growth factor-induced endocytosis of TWIK-related acid-sensitive K+ 1 channels in adrenal medullary cells and PC12 cells

  • Signaling and Cell Physiology
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Abstract

TWIK-related acid-sensitive K+ (TASK) channels belong to a family of two-pore domain K+ channels which produce background K+ currents and are involved in important physiological functions, such as acidosis detection. We have recently elucidated that TASK1-like channels function as a sensor of acidosis in rat adrenal medullary (AM) cells and thus are indispensable for the endocrine function of AM cells. Here, using pharmacological, electrophysiological and biochemical methods, we studied how the expression and localisation of TASK1 channels are regulated in rat AM cells and PC12 cells. PC12 cells were found to express not only TASK1 but also TASK3 channels, and they did not constitute a heterodimer. The exposure of AM cells and PC12 cells to nerve growth factor (NGF) induced endocytosis of TASK1, but not TASK3 channels, in a clathrin-dependent manner. Mutation analysis of the TASK1 channel revealed that the dileucine motif (LL263/264) was involved in at least part of the endocytosis. Plating GFP-TASK1-expressing PC12 cells onto a sheet of fibroblasts, which produced NGF, resulted in the endocytosis of GFP-TASK1 channels. Additionally, the expression of TASK1 channels at the protein and mRNA levels was suppressed in PC12 cells treated with NGF for 2 weeks. These results indicate that NGF suppresses the expression of TASK1 channels in the plasma membrane via not only endocytosis but also the inhibition of gene transcription. Thus, no access to NGF may play a major role for the maintenance of TASK1 channels in the cell membrane in AM cells.

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Acknowledgments

This work was supported in part by MEXT KAKENHI (21026029 to MI) and JSPS KAKENHI (21500360 to MI and 22790222 and 24790228 to HM). We would like to thank D.A. Bayliss (University of Virginia, USA) for providing GFP-TASK1 and GFP-TASK3 constructs, K. Kono (UOEH, Japan) for NIH3T3, B.J. Nichols (MRC Laboratory of Molecular Biology, UK) and M.A.M. Prado (Robarts Research Institute, Canada) for the AP180-C construct, S. Ferguson (Robarts Research Institute) for Rab5-GFP construct and M. Ymamoto (Fukushima Medical University, Japan) for Golgi-CFP construct. The mouse anti-LAMP2 Ab was obtained from the Developmental Studies Hybridoma Bank developed under the auspices of the NICHD and maintained by the University of Iowa. We are grateful to T. Hatama for technical assistance.

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The authors declare that they have on conflict of interest.

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Authors and Affiliations

  1. Department of Cell and Systems Physiology, University of Occupational and Environmental Health School of Medicine, Kitakyushu, 807-8555, Japan

    Hidetada Matsuoka, Keita Harada & Masumi Inoue

  2. Department of Psychiatry, University of Occupational and Environmental Health School of Medicine, Kitakyushu, 807-8555, Japan

    Jun Nakamura

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  1. Hidetada Matsuoka
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  2. Keita Harada
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  4. Masumi Inoue
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Correspondence to Masumi Inoue.

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Matsuoka, H., Harada, K., Nakamura, J. et al. Nerve growth factor-induced endocytosis of TWIK-related acid-sensitive K+ 1 channels in adrenal medullary cells and PC12 cells. Pflugers Arch - Eur J Physiol 465, 1051–1064 (2013). https://doi.org/10.1007/s00424-013-1222-3

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