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Reelin is a platelet protein and functions as a positive regulator of platelet spreading on fibrinogen

Abstract

Abnormalities of platelet functions have been linked to reelin-impaired neuronal disorders. However, little attention has been given to understanding the interplay between reelin and platelet. In this study, reelin was found to present in the human platelets and megakaryocyte-like leukemic cells. Reelin-binding assays revealed that extracellular reelin can interact with platelets through the receptor belonging to the low density lipoprotein receptor gene family. The reelin-to-platelet interactions enhance platelet spreading on fibrinogen concomitant with the augmentation of lamellipodia formation and F-actin bundling. In contrast, reelin has no effect on integrin αIIbβ3 activation and agonist-induced platelet aggregation. Molecular analysis revealed that the up-regulation of Rac1 activity and the inhibition of protein kinase C δ-Thr505 phosphorylation are important for reelin-mediated enhancement of platelet spreading on fibrinogen. These findings demonstrate for the first time that reelin is present in platelets and the reelin-to-platelet interactions play a novel role in platelet signaling and functions.

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Abbreviations

AA:

Arachidonic acid

ApoER2:

ApoE receptor 2

BSA:

Bovine serum albumin

DAB:

Disabled

FITC:

Fluorescein isothiocyanate

GST:

Glutathione-S-transferase

PBMC:

Peripheral blood mononuclear cell

PBS:

Phosphate-buffered saline

PF-4:

Platelet factor 4

PKCδ:

Protein kinase C δ

PGI2 :

Prostaglandin I2

PRP:

Platelet-rich-plasma

RAP:

Receptor-associated protein

SFKs:

SRC family tyrosine kinases

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Acknowledgments

This work was supported in part by the grants NHRI-EX98-9612BI, NSC 95-2320-B-182-023-MY3, CMRPD170132, EMRPD180171 and EMRPD180221 to C.P.T; CMU95-335 to J.C.C.

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Correspondence to Ju-Chien Cheng or Ching-Ping Tseng.

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Tseng, WL., Huang, CL., Chong, KY. et al. Reelin is a platelet protein and functions as a positive regulator of platelet spreading on fibrinogen. Cell. Mol. Life Sci. 67, 641–653 (2010). https://doi.org/10.1007/s00018-009-0201-5

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Keywords

  • Fibrinogen
  • Platelet spreading
  • PKCδ
  • Rac1
  • Reelin