Rab5 Is a Novel Regulator of Mast Cell Secretory Granules: Impact on Size, Cargo, and Exocytosis

Nurit P. Azouz, Neta Zur, Adi Efergan, Norihiko Ohbayashi, Mitsunori Fukuda, Dina Amihai, Ilan Hammel, Marc E. Rothenberg, Ronit Sagi-Eisenberg

    研究成果: Article査読

    34 被引用数 (Scopus)

    抄録

    Secretion of inflammatory mediators prestored in mast cells secretory granules (SGs) enhances immune responses such as in allergy and host defense. However, the mechanisms underlying the biogenesis of the SGs remain largely unresolved. By combining high-resolution live cell imaging and quantitative morphometric analyses, we show that the small GTPase Rab5 controls the SG size and cargo composition by a VAMP8-dependent fusion mechanism. Knockdown of the endogenous Rab5, or expression of constitutively negative mutants, significantly reduces the size of SGs and increases their number. Conversely, expression of constitutively active Rab5 mutants induces few, but giant, SGs. Both the small and giant SGs maintain their exocytosis competence. Finally, we show that Rab5-mediated fusion between Golgi-derived SGs and early endosomes precedes the maturation of the SGs, as reflected by the recruitment of Rab27B, and allows the incorporation of cargo, such as CD63, that traffics through endosomes. Collectively, our results assign Rab5 a key role in mediating mast cell SG fusion during biogenesis, thereby controlling the amount and composition of the SGs content and maintaining the communication between new and pre-existing SGs. The Journal of Immunology, 2014, 192: 4043-4053.

    本文言語English
    ページ(範囲)4043-4053
    ページ数11
    ジャーナルJournal of Immunology
    192
    9
    DOI
    出版ステータスPublished - 2014 5 1

    ASJC Scopus subject areas

    • 免疫アレルギー学
    • 免疫学

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