title: Laminin stimulates spreading of platelets through integrin alpha6beta1-dependent activation of GPVI.
abstract: The extracellular matrix protein, laminin, supports platelet adhesion through binding to integrin alpha6beta1 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 alpha6beta1 and the collagen receptor GPVI. The integrin alpha6beta1 is essential for adhesion to laminin, as demonstrated using an alpha6-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 alpha6beta1 Lamellipodia and filopodia formation are inhibited in Syk-deficient platelets, demonstrating a key role for the kinase in signaling downstream of GPVI and integrin alpha6beta1 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 alpha6beta1 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.
authors.affiliation: Department of Clinical and Laboratory Medicine, Yamanashi Medical University, 1110 Shimokato Tamaho Nakakoma, Yamanashi 409-3898, Japan. oinoue@yamanashi.ac.jp
authors.forename: Osamu
authors.initials: O
authors.lastname: Inoue
authors.forename: Katsue
authors.initials: K
authors.lastname: Suzuki-Inoue
authors.forename: Owen J T
authors.initials: OJ
authors.lastname: McCarty
authors.forename: Masaaki
authors.initials: M
authors.lastname: Moroi
authors.forename: Zaverio M
authors.initials: ZM
authors.lastname: Ruggeri
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Kunicki
authors.forename: Yukio
authors.initials: Y
authors.lastname: Ozaki
authors.forename: Steve P
authors.initials: SP
authors.lastname: Watson
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D005260:Female; D006801:Humans; D039121:Integrin alpha6beta1 / Q000502:physiology*; D007797:Laminin / Q000302:isolation & purification / Q000494:pharmacology*; D051379:Mice; D010920:Placenta; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism*; D011247:Pregnancy; D020349:Surface Plasmon Resonance
chemical_list: D039121:Integrin alpha6beta1; D007797:Laminin; D010980:Platelet Membrane Glycoproteins; C098341:platelet membrane glycoprotein VI