Rab5 is critical for SNAP23 regulated granule-granule fusion during compound exocytosis

Ofir Klein, Amit Roded, Neta Zur, Nurit P. Azouz, Olga Pasternak, Koret Hirschberg, Ilan Hammel, Paul A. Roche, Ayaka Yatsu, Mitsunori Fukuda, Stephen J. Galli, Ronit Sagi-Eisenberg

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    8 Citations (Scopus)

    Abstract

    Compound exocytosis is considered the most massive mode of exocytosis, during which the membranes of secretory granules (SGs) fuse with each other to form a channel through which the entire contents of their granules is released. The underlying mechanisms of compound exocytosis remain largely unresolved. Here we show that the small GTPase Rab5, a known regulator of endocytosis, is pivotal for compound exocytosis in mast cells. Silencing of Rab5 shifts receptor-triggered secretion from a compound to a full exocytosis mode, in which SGs individually fuse with the plasma membrane. Moreover, we show that Rab5 is essential for FcϵRI-triggered association of the SNARE protein SNAP23 with the SGs. Direct evidence is provided for SNAP23 involvement in homotypic SG fusion that occurs in the activated cells. Finally, we show that this fusion event is prevented by inhibition of the IKKβ2 kinase, however, neither a phosphorylation-deficient nor a phosphomimetic mutant of SNAP23 can mediate homotypic SG fusion in triggered cells. Taken together our findings identify Rab5 as a heretofore-unrecognized regulator of compound exocytosis that is essential for SNAP23-mediated granule-granule fusion. Our results also implicate phosphorylation cycles in controlling SNAP23 SNARE function in homotypic SG fusion.

    Original languageEnglish
    Article number15315
    JournalScientific reports
    Volume7
    Issue number1
    DOIs
    Publication statusPublished - 2017 Dec 1

    ASJC Scopus subject areas

    • General

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  • Cite this

    Klein, O., Roded, A., Zur, N., Azouz, N. P., Pasternak, O., Hirschberg, K., Hammel, I., Roche, P. A., Yatsu, A., Fukuda, M., Galli, S. J., & Sagi-Eisenberg, R. (2017). Rab5 is critical for SNAP23 regulated granule-granule fusion during compound exocytosis. Scientific reports, 7(1), [15315]. https://doi.org/10.1038/s41598-017-15047-8