Rab12 regulates retrograde transport of mast cell secretory granules by interacting with the RILP-dynein complex

Adi Efergan, Nurit P. Azouz, Ofir Klein, Kenta Noguchi, Marc E. Rothenberg, Mitsunori Fukuda, Ronit Sagi-Eisenberg

    Research output: Contribution to journalArticlepeer-review

    13 Citations (Scopus)

    Abstract

    Secretory granule (SG) transport is a critical step in regulated exocytosis including degranulation of activated mast cells. The latter process results in the release of multiple inflammatory mediators that play key roles in innate immunity, as well as in allergic responses. In this study, we identified the small GTPase Rab12 as a novel regulator of mast cell SG transport, and we provide mechanistic insights into its mode of action. We show that Rab12 is activated in a stimulus-dependent fashion and promotes microtubule-dependent retrograde transport of the SGs in the activated cells. We also show that this minus end transport of the SGs is mediated by the RILP-dynein complex and identify RILP as a novel effector of Rab12. Finally, we show that Rab12 negatively regulates mast cell degranulation. Taken together, our results identify Rab12 as a novel regulator of mast cell responses and disclose for the first time, to our knowledge, the mechanism of retrograde transport of the mast cell SGs.

    Original languageEnglish
    Pages (from-to)1091-1101
    Number of pages11
    JournalJournal of Immunology
    Volume196
    Issue number3
    DOIs
    Publication statusPublished - 2016 Feb 1

    ASJC Scopus subject areas

    • Immunology and Allergy
    • Immunology

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