Calcium-dependent activator protein for secretion 2 interacts with the class II ARF small GTPases and regulates dense-core vesicle trafficking

Authors

  • Tetsushi Sadakata,

    1.  Advanced Scientific Research Leaders Development Unit, Gunma University, Japan
    2.  Laboratory for Molecular Neurogenesis, RIKEN Brain Science Institute, Wako, Saitama, Japan
    3.  JST/CREST, Kawaguchi, Saitama, Japan
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  • Yukiko Sekine,

    1.  Laboratory for Molecular Neurogenesis, RIKEN Brain Science Institute, Wako, Saitama, Japan
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  • Megumi Oka,

    1.  Advanced Scientific Research Leaders Development Unit, Gunma University, Japan
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  • Makoto Itakura,

    1.  JST/CREST, Kawaguchi, Saitama, Japan
    2.  Department of Biochemistry, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan
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  • Masami Takahashi,

    1.  JST/CREST, Kawaguchi, Saitama, Japan
    2.  Department of Biochemistry, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan
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  • Teiichi Furuichi

    1.  Laboratory for Molecular Neurogenesis, RIKEN Brain Science Institute, Wako, Saitama, Japan
    2.  JST/CREST, Kawaguchi, Saitama, Japan
    3.  Department of Applied Biological Science, Tokyo University of Science, Noda, Chiba, Japan
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T. Furuichi, Applied Biological Science, Faculty of Science and Technology, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan
Fax: +81 4 7124 2150
Tel: +81 4 7124 1501 ext. 3459
E-mail: tfuruichi@rs.tus.ac.jp

Abstract

The Ca2+-dependent activator protein for secretion (CAPS) family consists of two members (CAPS1 and CAPS2) and regulates the exocytosis of catecholamine-containing or neuropeptide-containing dense-core vesicles (DCVs) at secretion sites such as nerve terminals. A large fraction of CAPS1, however, is localized in the cell soma, and we have recently shown the possible involvement of somal CAPS1 in DCV trafficking in the trans-Golgi network. CAPS1 and CAPS2 are differentially expressed in various regions of the mouse brain but exhibit similar expression patterns in other tissues, such as the spleen. Thus, in the present study we analyzed whether CAPS2 displays similar subcellular localization and functional roles in the cell soma as CAPS1. We found that somal CAPS2 is associated with the Golgi membrane, and mediates binding and recruitment of the GDP-bound form of ARF4 and ARF5 (members of the membrane-trafficking small GTPase family) to the Golgi membrane. CAPS2 knockdown and overexpression of CAPS2-binding-deficient ARF4/ARF5 both induced accumulation of the DCV resident protein chromogranin A around the Golgi apparatus. CAPS2 knockout mice have dilated trans-Golgi structures when viewed by electron microscopy. These results for CAPS2 strongly support our idea that the CAPS family proteins exert dual roles in DCV trafficking, mediating trafficking at both the secretion site for exocytosis and at the Golgi complex for biogenesis.

Structured digital abstract

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