Unknown

Dataset Information

0

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


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 Fc?RI-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 IKK?2 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.

SUBMITTER: Klein O 

PROVIDER: S-EPMC5681557 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

altmetric image

Publications

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

Klein Ofir O   Roded Amit A   Zur Neta N   Azouz Nurit P NP   Pasternak Olga O   Hirschberg Koret K   Hammel Ilan I   Roche Paul A PA   Yatsu Ayaka A   Fukuda Mitsunori M   Galli Stephen J SJ   Sagi-Eisenberg Ronit R  

Scientific reports 20171110 1


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  ...[more]

Similar Datasets

| S-EPMC6736185 | biostudies-literature
| S-EPMC3573216 | biostudies-literature
| S-EPMC4534191 | biostudies-literature
| S-EPMC10284390 | biostudies-literature
| S-EPMC438965 | biostudies-literature
| S-EPMC9265163 | biostudies-literature
| S-EPMC2878813 | biostudies-literature
| S-EPMC519157 | biostudies-literature
| S-EPMC5507579 | biostudies-literature
| S-EPMC6805152 | biostudies-literature