Laminin stimulates spreading of platelets through integrin α6β1-dependent activation of GPVI

Osamu Inoue, Katsue Suzuki-Inoue, Owen McCarty, Masaaki Moroi, Zaverio M. Ruggeri, Thomas J. Kunicki, Yukio Ozaki, Steve P. Watson

Research output: Contribution to journalArticle

111 Citations (Scopus)

Abstract

The extracellular matrix protein, laminin, supports platelet adhesion through binding to integrin α6β1 In the present study, we demonstrate that human laminin, purified from placenta, also stimulates formation of filopodia and lamellipodia in human and mouse platelets through a pathway that is dependent on α6β1 and the collagen receptor GPVI. The integrin α6β1 is essential for adhesion to laminin, as demonstrated using an α6-blocking antibody, whereas GPVI is dispensable for this response, as shown using "knockout" mouse platelets. On the other hand, lamellipodia formation on laminin is completely inhibited in the absence of GPVI, although filopodia formation remains and is presumably mediated via α6β1 Lamellipodia and filopodia formation are inhibited in Syk-deficient platelets, demonstrating a key role for the kinase in signaling downstream of GPVI and integrin α6β1 GPVI was confirmed as a receptor for laminin using surface plasmon resonance spectroscopy and by demonstration of lamellipodia formation on laminin in the presence of collagenase. These results identify GPVI as a novel receptor for laminin and support a model in which integrin α6β 1 brings laminin to GPVI, which in turn mediates lamellipodia formation. We speculate that laminin contributes to platelet spreading in vivo through a direct interaction with GPVI.

Original languageEnglish (US)
Pages (from-to)1405-1412
Number of pages8
JournalBlood
Volume107
Issue number4
DOIs
StatePublished - Feb 15 2006
Externally publishedYes

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Pseudopodia
Laminin
Platelets
Integrins
Blood Platelets
Chemical activation
Laminin Receptors
Adhesion
Blocking Antibodies
Extracellular Matrix Proteins
Surface plasmon resonance
Collagenases
Surface Plasmon Resonance
Knockout Mice
Placenta
Phosphotransferases
Demonstrations
Spectrum Analysis
Spectroscopy

ASJC Scopus subject areas

  • Hematology

Cite this

Inoue, O., Suzuki-Inoue, K., McCarty, O., Moroi, M., Ruggeri, Z. M., Kunicki, T. J., ... Watson, S. P. (2006). Laminin stimulates spreading of platelets through integrin α6β1-dependent activation of GPVI. Blood, 107(4), 1405-1412. https://doi.org/10.1182/blood-2005-06-2406

Laminin stimulates spreading of platelets through integrin α6β1-dependent activation of GPVI. / Inoue, Osamu; Suzuki-Inoue, Katsue; McCarty, Owen; Moroi, Masaaki; Ruggeri, Zaverio M.; Kunicki, Thomas J.; Ozaki, Yukio; Watson, Steve P.

In: Blood, Vol. 107, No. 4, 15.02.2006, p. 1405-1412.

Research output: Contribution to journalArticle

Inoue, O, Suzuki-Inoue, K, McCarty, O, Moroi, M, Ruggeri, ZM, Kunicki, TJ, Ozaki, Y & Watson, SP 2006, 'Laminin stimulates spreading of platelets through integrin α6β1-dependent activation of GPVI', Blood, vol. 107, no. 4, pp. 1405-1412. https://doi.org/10.1182/blood-2005-06-2406
Inoue, Osamu ; Suzuki-Inoue, Katsue ; McCarty, Owen ; Moroi, Masaaki ; Ruggeri, Zaverio M. ; Kunicki, Thomas J. ; Ozaki, Yukio ; Watson, Steve P. / Laminin stimulates spreading of platelets through integrin α6β1-dependent activation of GPVI. In: Blood. 2006 ; Vol. 107, No. 4. pp. 1405-1412.
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