ELMO1 deficiency enhances platelet function

Blood Advances
Akruti PatelSatya P Kunapuli

Abstract

Phosphatidylinositol 3-kinase is an important signaling molecule that, once activated, leads to the generation of phosphatidylinositol (3,4,5)-trisphosphate (PIP3). We performed a proteomic screen to identify PIP3-interacting proteins in human platelets. Among these proteins, we found engulfment and cell motility 1 (ELMO1), a scaffold protein with no catalytic activity. ELMO1 is expressed in platelets and interacts with active RhoG. However, the function of ELMO1 in platelets is not known. The focus of this study was to determine the function of ELMO1 in platelets utilizing ELMO1-/- mice. Platelet aggregation, granule secretion, integrin αIIbβ3 activation, and thromboxane generation were enhanced in ELMO1-/- platelets in response to glycoprotein VI (GPVI) agonists but unaltered when a protease-activated receptor 4 agonist was used. The kinetics of spreading on immobilized fibrinogen was enhanced in ELMO1-/- platelets compared with wild-type (WT) littermate controls. This suggests that ELMO1 plays a role downstream of the GPVI and integrin αIIbβ3 pathway. Furthermore, whole blood from ELMO1-/- mice perfused over collagen exhibited enhanced thrombus formation compared with WT littermate controls. ELMO1-/- mice showed reduced surv...Continue Reading

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Citations

Feb 1, 2020·Clinical and Translational Medicine·Tom N Durrant, Ingeborg Hers
Nov 27, 2020·The Biochemical Journal·Agnès RibesBernard Payrastre
May 2, 2021·The Journal of Biological Chemistry·John C KostyakSatya P Kunapuli

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