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Mouse platelet Ral GTPases control P-selectin surface expression, regulating platelet-leukocyte interaction

Research output: Contribution to journalArticle

Original languageEnglish
Pages (from-to)787-800
Number of pages14
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume38
Issue number4
Early online date8 Feb 2018
DOIs
DateAccepted/In press - 25 Jan 2018
DateE-pub ahead of print - 8 Feb 2018
DatePublished (current) - 1 Apr 2018

Abstract

Objective - RalA and RalB GTPases are important regulators of cell growth, cancer metastasis, and granule secretion. The purpose of this study was to determine the role of Ral GTPases in platelets with the use of platelet-specific gene-knockout mouse models. Approach and Results - This study shows that platelets from double knockout mice, in which both GTPases have been deleted, show markedly diminished (≈85% reduction) P-selectin translocation to the surface membrane, suggesting a critical role in α-granule secretion. Surprisingly, however, there were only minor effects on stimulated release of soluble α- and δ-granule content, with no alteration in granule count, morphology, or content. In addition, their expression was not essential for platelet aggregation or thrombus formation. However, absence of surface P-selectin caused a marked reduction (≈70%) in platelet-leukocyte interactions in blood from RalAB double knockout mice, suggesting a role for platelet Rals in platelet-mediated inflammation. Conclusions - Platelet Ral GTPases primarily control P-selectin surface expression, in turn regulating platelet-leukocyte interaction. Ral GTPases could therefore be important novel targets for the selective control of platelet-mediated immune cell recruitment and inflammatory disease.

    Research areas

  • Platelets, Cell Signaling/Signal Transduction, Inflammation

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    Rights statement: This is the author accepted manuscript (AAM). The final published version (version of record) is available online via AHA Inc. at http://atvb.ahajournals.org/content/38/4/787/tab-article-info. Please refer to any applicable terms of use of the publisher.

    Accepted author manuscript, 40 MB, PDF document

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