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

Research output: Contribution to journalArticlepeer-review

41 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)4043-4053
Number of pages11
JournalJournal of Immunology
Volume192
Issue number9
DOIs
Publication statusPublished - 2014 May 1

Fingerprint

Dive into the research topics of 'Rab5 Is a Novel Regulator of Mast Cell Secretory Granules: Impact on Size, Cargo, and Exocytosis'. Together they form a unique fingerprint.

Cite this