The PI 3-kinase PI3KC2α regulates mouse platelet membrane structure and function independently of membrane lipid composition.
Fiche publication
Date publication
novembre 2018
Journal
FEBS letters
Auteurs
Membres identifiés du Cancéropôle Est :
Dr GACHET Christian
Tous les auteurs :
Selvadurai MV, Brazilek RJ, Moon MJ, Rinckel JY, Eckly A, Gachet C, Meikle PJ, Nandurkar HH, Nesbitt WS, Hamilton JR
Lien Pubmed
Résumé
PI3KC2α is a phosphoinositide 3-kinase with a recently reported function in platelets; PI3KC2α-deficient mouse platelets have altered membrane structure and impaired function. Yet, how these membrane changes cause platelet dysfunction remains unknown. Here, focused ion beam-scanning electron microscopy of PI3KC2α-deficient platelet ultrastructure reveals a specific effect on the internal membrane structure, while liquid chromatography-tandem mass spectrometry profiling of 294 lipid species shows unaltered lipid composition. Functionally, PI3KC2α-deficient platelets exhibit impaired thrombosis specifically under conditions involving membrane tethering. These studies indicate that the structural changes in PI3KC2α-deficient platelets are limited to the membrane, occur without major changes in lipid composition, and selectively impair cell function during thrombus formation. These findings illustrate a unique mechanism that may be targetable for anti-thrombotic benefit. This article is protected by copyright. All rights reserved.
Mots clés
open canalicular system, phosphoinositide 3-kinase, platelets, thrombosis
Référence
FEBS Lett.. 2018 Nov 12;: