Munc13-4 Is a GTP-Rab27-binding Protein Regulating Dense Core Granule Secretion in Platelets

Ryutaro Shirakawa, Tomohito Higashi, Arata Tabuchi, Akira Yoshioka, Hiroaki Nishioka, Mitsunori Fukuda, Toru Kita, Hisanori Horiuchi

Research output: Contribution to journalArticlepeer-review

159 Citations (Scopus)

Abstract

Platelets store self-agonists such as ADP and serotonin in dense core granules. Although exocytosis of these granules is crucial for hemostasis and thrombosis, the underlying mechanism is not fully understood. Here, we show that incubation of permeabilized platelets with unprenylated active mutant Rab27A-Q78L, wild type Rab27A, and Rab27B inhibited the secretion, whereas inactive mutant Rab27A-T23N and other GTPases had no effects. Furthermore, we affinity-purified a GTP-Rab27A-binding protein in platelets and identified it as Munc13-4, a homologue of Munc13-1 known as a priming factor for neurotransmitter release. Recombinant Munc13-4 directly bound to GTP-Rab27A and -Rab27B in vitro, but not other GTPases, and enhanced secretion in an in vitro assay. The inhibition of secretion by unprenylated Rab27A was rescued by the addition of Munc13-4, suggesting that Munc13-4 mediates the function of GTP-Rab27. Thus, Rab27 regulates the dense core granule secretion in platelets by employing its binding protein, Munc13-4.

Original languageEnglish
Pages (from-to)10730-10737
Number of pages8
JournalJournal of Biological Chemistry
Volume279
Issue number11
DOIs
Publication statusPublished - 2004 Mar 12
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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