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The PI 3‐kinase PI 3 KC 2α regulates mouse platelet membrane structure and function independently of membrane lipid composition
Author(s) -
Selvadurai Maria V.,
Brazilek Rose J.,
Moon Mitchell J.,
Rinckel JeanYves,
Eckly Anita,
Gachet Christian,
Meikle Peter J.,
Nandurkar Harshal H.,
Nesbitt Warwick S.,
Hamilton Justin R.
Publication year - 2019
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.13295
Subject(s) - platelet , chemistry , microbiology and biotechnology , biochemistry , membrane , biology , immunology
PI 3 KC 2α is a phosphoinositide 3‐kinase with a recently reported function in platelets; PI 3 KC 2α‐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 PI 3 KC 2α‐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, PI 3 KC 2α‐deficient platelets exhibit impaired thrombosis specifically under conditions involving membrane tethering. These studies indicate that the structural changes in PI 3 KC 2α‐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.