4F2hc stabilizes GLUT1 protein and increases glucose transport activity

Haruya Ohno, Yusuke Nakatsu, Hideyuki Sakoda, Akifumi Kushiyama, Hiraku Ono, Midori Fujishiro, Yuichiro Otani, Hirofumi Okubo, Masayasu Yoneda, Toshiaki Fukushima, Yoshihiro Tsuchiya, Hideaki Kamata, Fusanori Nishimura, Hiroki Kurihara, Hideki Katagiri, Yoshitomo Oka, Tomoichiro Asano

研究成果: Contribution to journalArticle査読

21 被引用数 (Scopus)

抄録

Glucose transporter 1 (GLUT1) is widely distributed throughout various tissues and contributes to insulin- independent basal glucose uptake. Using a split-ubiquitin membrane yeast two-hybrid system, we newly identified 4F2 heavy chain (4F2hc) as a membrane protein interacting with GLUT1. Though 4F2hc reportedly forms heterodimeric complexes between amino acid transporters, such as LAT1 and LAT2, and regulates amino acid uptake, we investigated the effects of 4F2hc on GLUT1 expression and the associated glucose uptake. First, FLAG-tagged 4F2hc and hemagglutinin-tagged GLUT1 were overexpressed in human embryonic kidney 293 cells and their association was confirmed by coimmunoprecipitation. The green fluorescent protein-tagged 4F2hc and DsRed-tagged GLUT1 showed significant, but incomplete, colocalization at the plasma membrane. In addition, an endogenous association between GLUT1 and 4F2hc was demonstrated using mouse brain tissue and HeLa cells. Interestingly, overexpression of 4F2hc increased the amount of GLUT1 protein in HeLa and HepG2 cells with increased glucose uptake. In contrast, small interfering RNA (siRNA)-mediated 4F2hc gene suppression markedly reduced GLUT1 protein in both cell types, with reduced glucose uptake. While GLUT1 mRNA levels were not affected by overexpression or gene silencing of 4F2hc, GLUT1 degradation after the addition of cycloheximide was significantly suppressed by 4F2hc overexpression and increased by 4F2hc siRNA treatment. Taken together, these observations indicate that 4F2hc is likely to be involved in GLUT1 stabilization and to contribute to the regulation of not only amino acid but also glucose metabolism.

本文言語英語
ページ(範囲)C1047-C1054
ジャーナルAmerican Journal of Physiology - Cell Physiology
300
5
DOI
出版ステータス出版済み - 5 2011
外部発表はい

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cell Biology

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