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

Maria V. Selvadurai, Rose J. Brazilek, Mitchell J. Moon, Jean Yves Rinckel, Anita Eckly, Christian Gachet, Peter J. Meikle, Harshal H. Nandurkar, Warwick S. Nesbitt, Justin R. Hamilton

Research output: Contribution to journalArticleResearchpeer-review

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 languageEnglish
Pages (from-to)88-96
Number of pages9
JournalFEBS Letters
Volume593
Issue number1
DOIs
Publication statusPublished - 1 Jan 2019

Keywords

  • open canalicular system
  • phosphoinositide 3-kinase
  • platelets
  • thrombosis

Cite this

Selvadurai, Maria V. ; Brazilek, Rose J. ; Moon, Mitchell J. ; Rinckel, Jean Yves ; Eckly, Anita ; Gachet, Christian ; Meikle, Peter J. ; Nandurkar, Harshal H. ; Nesbitt, Warwick S. ; Hamilton, Justin R. / The PI 3-kinase PI3KC2α regulates mouse platelet membrane structure and function independently of membrane lipid composition. In: FEBS Letters. 2019 ; Vol. 593, No. 1. pp. 88-96.
@article{a5f5e8ca30f24f8fab6c13789bd0c55a,
title = "The PI 3-kinase PI3KC2α regulates mouse platelet membrane structure and function independently of membrane lipid composition",
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.",
keywords = "open canalicular system, phosphoinositide 3-kinase, platelets, thrombosis",
author = "Selvadurai, {Maria V.} and Brazilek, {Rose J.} and Moon, {Mitchell J.} and Rinckel, {Jean Yves} and Anita Eckly and Christian Gachet and Meikle, {Peter J.} and Nandurkar, {Harshal H.} and Nesbitt, {Warwick S.} and Hamilton, {Justin R.}",
year = "2019",
month = "1",
day = "1",
doi = "10.1002/1873-3468.13295",
language = "English",
volume = "593",
pages = "88--96",
journal = "FEBS Letters",
issn = "0014-5793",
publisher = "Wiley-Blackwell",
number = "1",

}

The PI 3-kinase PI3KC2α regulates mouse platelet membrane structure and function independently of membrane lipid composition. / Selvadurai, Maria V.; Brazilek, Rose J.; Moon, Mitchell J.; Rinckel, Jean Yves; Eckly, Anita; Gachet, Christian; Meikle, Peter J.; Nandurkar, Harshal H.; Nesbitt, Warwick S.; Hamilton, Justin R.

In: FEBS Letters, Vol. 593, No. 1, 01.01.2019, p. 88-96.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - The PI 3-kinase PI3KC2α regulates mouse platelet membrane structure and function independently of membrane lipid composition

AU - Selvadurai, Maria V.

AU - Brazilek, Rose J.

AU - Moon, Mitchell J.

AU - Rinckel, Jean Yves

AU - Eckly, Anita

AU - Gachet, Christian

AU - Meikle, Peter J.

AU - Nandurkar, Harshal H.

AU - Nesbitt, Warwick S.

AU - Hamilton, Justin R.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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.

AB - 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.

KW - open canalicular system

KW - phosphoinositide 3-kinase

KW - platelets

KW - thrombosis

UR - http://www.scopus.com/inward/record.url?scp=85057110479&partnerID=8YFLogxK

U2 - 10.1002/1873-3468.13295

DO - 10.1002/1873-3468.13295

M3 - Article

VL - 593

SP - 88

EP - 96

JO - FEBS Letters

JF - FEBS Letters

SN - 0014-5793

IS - 1

ER -