Rab12 Regulates Retrograde Transport of Mast Cell Secretory Granules by Interacting with the RILP-Dynein Complex

J Immunol. 2016 Feb 1;196(3):1091-101. doi: 10.4049/jimmunol.1500731. Epub 2016 Jan 6.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / immunology
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Animals
  • Blotting, Western
  • Cell Degranulation / immunology*
  • Cell Line
  • Dyneins / immunology
  • Dyneins / metabolism*
  • Immunohistochemistry
  • Immunoprecipitation
  • Mast Cells / immunology
  • Mast Cells / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Microscopy, Confocal
  • Protein Transport / immunology
  • Rats
  • Real-Time Polymerase Chain Reaction
  • Secretory Vesicles / immunology
  • Secretory Vesicles / metabolism*
  • Transfection
  • rab GTP-Binding Proteins / immunology
  • rab GTP-Binding Proteins / metabolism*


  • Adaptor Proteins, Signal Transducing
  • RILP protein, rat
  • rab12 protein, rat
  • Dyneins
  • rab GTP-Binding Proteins