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Rab8a is involved in membrane trafficking of Kir6.2 in the MIN6 insulinoma cell line

Authors
  • Uchida, Keiichiro1, 2
  • Nomura, Masatoshi3
  • Yamamoto, Tadashi1
  • Ogawa, Yoshihiro2, 4
  • Teramoto, Noriyoshi1, 5
  • 1 Saga University, Department of Pharmacology, Faculty of Medicine, Saga, 849-8501, Japan , Saga (Japan)
  • 2 Kyushu University, Department of Medicine and Bioregulatory Science, Graduate School of Medical Science, Fukuoka, 812-8582, Japan , Fukuoka (Japan)
  • 3 Kurume University, Division of Endocrinology and Metabolism, Department of Internal Medicine, School of Medicine, Kurume, 830-0011, Japan , Kurume (Japan)
  • 4 Tokyo Medical and Dental University, Department of Molecular and Cellular Metabolism, Graduate School of Medical and Dental Sciences, Tokyo, 113-8510, Japan , Tokyo (Japan)
  • 5 Tohoku University, Laboratory of Biomedical Engineering, Graduate School of Biomedical Engineering, Sendai, Japan , Sendai (Japan)
Type
Published Article
Journal
Pflügers Archiv - European Journal of Physiology
Publisher
Springer-Verlag
Publication Date
Jan 10, 2019
Volume
471
Issue
6
Pages
877–887
Identifiers
DOI: 10.1007/s00424-018-02252-1
Source
Springer Nature
Keywords
License
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Abstract

Although ATP-sensitive K+ (KATP) channels play an important role in the secretion of insulin by pancreatic beta cells, the mechanisms that regulate the intracellular transport of KATP channel subunit proteins (i.e., Kir6.2 and sulfonylurea receptor 1 (SUR1)) to the plasma membrane remain uncharacterized. We investigated the possibility that an interaction between KATP channel subunit proteins and Rab8a protein, a member of the RAS superfamily, may be involved in the membrane trafficking of KATP channels. Co-immunoprecipitation and immunostaining experiments using co-expression systems with fluorescent protein-tagged Kir6.2 were carried out to identify the coupling of KATP channels and Rab8a proteins in the insulin-secreting cell line, MIN6. Rab8a protein co-localized with Kir6.2 protein, a channel pore subunit (in a granular pattern), and with insulin. Knockdown of the Rab8a gene with RNA interference using small interfering RNA systems caused reductions in the amount of total KATP and plasma membrane surface KATP channels without decreasing the messenger RNA transcription of the KATP channel subunits. Rab8a gene knockdown also enhanced glucose-induced insulin secretion. These results suggest that Rab8a may be involved in membrane trafficking of KATP channels and the maintenance of normal insulin secretion in the MIN6 pancreatic beta cell line.

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