Journal article
The PI 3-kinase PI3KC2α regulates mouse platelet membrane structure and function independently of membrane lipid composition
MV Selvadurai, RJ Brazilek, MJ Moon, JY Rinckel, A Eckly, C Gachet, PJ Meikle, HH Nandurkar, WS Nesbitt, JR Hamilton
FEBS Letters | WILEY | Published : 2019
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 structur..
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Awarded by RMIT University
Funding Acknowledgements
Microfluidic devices were fabricated within the Micro Nano Research facility, RMIT University. We thank Monique Freund, Catherine Strassel, Fabienne Proamer and Neslihan Ulas for technical support; the staff of AMREP animal services for animal husbandry and care; staff of the Ramaciotti Centre for Cryo-Electron Microscopy and Monash Micro Imaging (Monash University) for assistance with microscopy; Jacqui Weir and Natalie Mellett for assistance with LC-MS; and Andrew Yett for interesting insights. This work was supported by grants to JRH from the National Health Medical Research Council of Australia (1047295 and 1120522), Australian Research Council (FT130100540), and CASS Foundation (SM/16/7334).