The PI 3-kinase PI3KC2α regulates mouse platelet membrane structure and function independently of membrane lipid composition

FEBS Letters

article

Maria V. Selvadurai¹  Rose J. Brazilek¹  Mitchell J. Moon¹  Jean-Yves Rinckel²  Anita Eckly²  Christian Gachet²  Peter J. Meikle³  Harshal H. Nandurkar¹  Warwick S. Nesbitt¹  Justin R. Hamilton¹ 

[1] Australian Centre for Blood Diseases, Monash University;Université de Strasbourg;Metabolomics Laboratory, Baker IDI Heart and Diabetes Institute;Microplatforms Research Group, School of Engineering, RMIT University

关键词: open canalicular system;    phosphoinositide 3-kinase;    platelets;    thrombosis;   

DOI  :  10.1002/1873-3468.13295

来源: John Wiley & Sons Ltd.

【 摘 要 】

PI3KC2a is a phosphoinositide 3-kinase with a recently reported function in platelets; PI3KC2a-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 PI3KC2a-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, PI3KC2a-deficient platelets exhibit impaired thrombosis specifically under conditions involving membrane tethering. These studies indicate that the structural changes in PI3KC2a-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.

【 授权许可】

Unknown