Get access

Nuclear localization of diacylglycerol kinase ζ in neurons

Authors

  • Yasukazu Hozumi,

    1. Department of Anatomy and Cell Biology, Yamagata University School of Medicine, Iida-nishi 2-2-2, Yamagata 990–9585, Japan
    2. Department of Otorhinolaryngology, Yamagata University School of Medicine, Iida-nishi 2-2-2, Yamagata 990–9585, Japan
    Search for more papers by this author
  • Tsukasa Ito,

    1. Department of Anatomy and Cell Biology, Yamagata University School of Medicine, Iida-nishi 2-2-2, Yamagata 990–9585, Japan
    2. Department of Otorhinolaryngology, Yamagata University School of Medicine, Iida-nishi 2-2-2, Yamagata 990–9585, Japan
    Search for more papers by this author
  • Tomoyuki Nakano,

    1. Department of Anatomy and Cell Biology, Yamagata University School of Medicine, Iida-nishi 2-2-2, Yamagata 990–9585, Japan
    Search for more papers by this author
  • Tamotsu Nakagawa,

    1. Division of Histology, Department of Cell Biology, Tohoku University Graduate School of Medicine, Seiryo-cho 2–1, Sendai 980–8575, Japan
    Search for more papers by this author
  • Masaru Aoyagi,

    1. Department of Otorhinolaryngology, Yamagata University School of Medicine, Iida-nishi 2-2-2, Yamagata 990–9585, Japan
    Search for more papers by this author
  • Hisatake Kondo,

    1. Division of Histology, Department of Cell Biology, Tohoku University Graduate School of Medicine, Seiryo-cho 2–1, Sendai 980–8575, Japan
    Search for more papers by this author
  • Kaoru Goto

    1. Department of Anatomy and Cell Biology, Yamagata University School of Medicine, Iida-nishi 2-2-2, Yamagata 990–9585, Japan
    Search for more papers by this author

: Dr Kaoru Goto, 1Department of Anatomy and Cell Biology, as above.
E-mail: kgoto@med.id.yamagata-u.ac.jp

Abstract

Diacylglycerol kinase (DGK) is involved in intracellular signal transduction as a regulator of levels of diacylglycerol which leads to protein kinase C activation. Previous studies have revealed that DGK consists of a family of isozymes in mammalian species and that most if not all of them show abundant expression in the central nervous system, suggesting the importance of this enzyme in neuronal function. Among the isozymes, DGKζ (previously also known as DGK-IV for the rat clone) has unique structural features, such as four ankyrin-like repeats and a nuclear localization signal (NLS), and shows intense mRNA expression in neurons of the olfactory bulb, hippocampus and cerebral and cerebellar cortices (Goto, K. & Kondo, H. (1996), Proc. Natl Acad. Sci. USA, 93, 11196–11201). However, previous studies have given conflicting results about whether or not DGKζ localizes to the nucleus in these cells. In this study, we have used immunohistochemistry with specific antibodies in brain tissues and cDNA transfection into primary cultured neurons to address this question. We have shown that, while DGKζ is primarily a nuclear protein in neurons, it can also be cytoplasmic in some conditions, and the subcellular location depends not only on the cell type but also on the developmental state or growth conditions of the cell. In addition, we have used deletion mutants to show that nuclear transport of DGKζ depends on a cooperative interaction between the NLS and the C-terminal region including ankyrin repeats in a manner which suggests that the NLS is a cryptic site whose exposure is regulated by the C-terminal region. Together, these results support the hypothesis that the localization of DGKζ may be regulated by differential expression of these various proteins which interact with its C-terminal region.

Ancillary