Regulation of platelet dense granule secretion by the Ral GTPase-exocyst pathway

Mitsunori Kawato, Ryutaro Shirakawa, Hirokazu Kondo, Tomohito Higashi, Tomoyuki Ikeda, Katsuya Okawa, Shuya Fukai, Osamu Nureki, Toru Kita, Hisanori Horiuchi

Research output: Contribution to journalArticlepeer-review

32 Citations (Scopus)

Abstract

Non-hydrolyzable GTP analogues, such as guanosine 5′-(β,γ- imido)triphosphate (GppNHp), induce granule secretion from permeabilized platelets in the absence of increased intracellular Ca2+. Here, we show that the GppNHp-induced dense granule secretion from permeabilized platelets occurred concomitantly with the activation of small GTPase Ral. This secretion was inhibited by the addition of GTP-Ral-binding domain (RBD) of Sec5, which is a component of the exocyst complex known to function as a tethering factor at the plasma membrane for vesicles. We generated an antibody against Sec5-RBD, which abolished the interaction between GTP-Ral and the exocyst complex in vitro. The addition of this antibody inhibited the GppNHp-induced secretion. These data indicate that Ral mediates the GppNHp-induced dense granule secretion from permeabilized platelets through interaction with its effector, the exocyst complex. Furthermore, GppNHp enhanced the Ca2+ sensitivity of dense granule secretion from permeabilized platelets, and this enhancement was inhibited by Sec5-RBD. In intact platelets, the association between Ral and the exocyst complex was induced by thrombin stimulation with a time course similar to that of dense granule secretion and Ral activation. Taken together, our results suggest that the Ral-exocyst pathway participates in the regulation of platelet dense granule secretion by enhancing the Ca2+ sensitivity of the secretion.

Original languageEnglish
Pages (from-to)166-174
Number of pages9
JournalJournal of Biological Chemistry
Volume283
Issue number1
DOIs
Publication statusPublished - 2008 Jan 4

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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