Projects per year
Abstract
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.
Original language | English |
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Pages (from-to) | 88-96 |
Number of pages | 9 |
Journal | FEBS Letters |
Volume | 593 |
Issue number | 1 |
DOIs | |
Publication status | Published - 1 Jan 2019 |
Keywords
- open canalicular system
- phosphoinositide 3-kinase
- platelets
- thrombosis
Projects
- 3 Finished
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Targeting oxidant-dependent pathways to improve stroke outcomes in COPD
Vlahos, R., Bozinovski, S., Crack, P. J., Miller, A., Hamilton, J., Irving, L. B. & Steinfort, D. P.
1/01/17 → 31/12/20
Project: Research
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Examining novel cell signalling in the regulation of platelet structure and function
Australian Research Council (ARC)
1/01/14 → 31/12/17
Project: Research
Equipment
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Monash Micro Imaging
Stephen Firth (Manager), Alex Fulcher (Operator), Oleks Chernyavskiy (Operator), Margaret Rzeszutek (Other), David Potter (Manager), Volker Hilsenstein (Operator), Juan Nunez-Iglesias (Other), Stephen Cody (Manager), Irena Carmichael (Operator), Betty Kouskousis (Other), Sarah Creed (Manager) & Giulia Ballerin (Operator)
Faculty of Medicine Nursing and Health Sciences Research PlatformsFacility/equipment: Facility
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Ramaciotti Centre for Cryo-Electron Microscopy
Georg Ramm (Manager), Simon Andrew Crawford (Operator), Hariprasad Venugopal (Operator), Joan Marea Clark (Operator) & Gediminas Gervinskas (Operator)
Faculty of Medicine Nursing and Health Sciences Research PlatformsFacility/equipment: Facility