title: Rap1-GTP-interacting adaptor molecule (RIAM) is dispensable for platelet integrin activation and function in mice.
abstract: Platelet aggregation at sites of vascular injury is essential for hemostasis but also thrombosis. Platelet adhesiveness is critically dependent on agonist-induced inside-out activation of heterodimeric integrin receptors by a mechanism involving the recruitment of talin-1 to the cytoplasmic integrin tail. Experiments in heterologous cells have suggested a critical role of Rap1-guanosine triphosphate-interacting adaptor molecule (RIAM) for talin-1 recruitment and thus integrin activation, but direct in vivo evidence to support this has been missing. We generated RIAM-null mice and found that they are viable, fertile, and apparently healthy. Unexpectedly, platelets from these mice show unaltered β3- and β1-integrin activation and consequently normal adhesion and aggregation responses under static and flow conditions. Similarly, hemostasis and arterial thrombus formation were indistinguishable between wild-type and RIAM-null mice. These results reveal that RIAM is dispensable for integrin activation and function in mouse platelets, strongly suggesting the existence of alternative mechanisms of talin-1 recruitment.
authors.affiliation: Department of Experimental Biomedicine, University Hospital and Rudolf Virchow Center, University of Würzburg, Würzburg, Germany.
authors.forename: Simon
authors.identifier: http://orcid.org/0000-0002-4299-4934
authors.initials: S
authors.lastname: Stritt
authors.affiliation: Department of Experimental Biomedicine, University Hospital and Rudolf Virchow Center, University of Würzburg, Würzburg, Germany.
authors.forename: Karen
authors.initials: K
authors.lastname: Wolf
authors.affiliation: Department of Experimental Biomedicine, University Hospital and Rudolf Virchow Center, University of Würzburg, Würzburg, Germany.
authors.forename: Viola
authors.initials: V
authors.lastname: Lorenz
authors.affiliation: Department of Experimental Biomedicine, University Hospital and Rudolf Virchow Center, University of Würzburg, Würzburg, Germany.
authors.forename: Timo
authors.initials: T
authors.lastname: Vögtle
authors.affiliation: Department of Experimental Biomedicine, University Hospital and Rudolf Virchow Center, University of Würzburg, Würzburg, Germany.
authors.forename: Shuchi
authors.initials: S
authors.lastname: Gupta
authors.affiliation: Department of Experimental Biomedicine, University Hospital and Rudolf Virchow Center, University of Würzburg, Würzburg, Germany.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Bösl
authors.affiliation: Department of Experimental Biomedicine, University Hospital and Rudolf Virchow Center, University of Würzburg, Würzburg, Germany.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Nieswandt
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D001792:Blood Platelets / Q000378:metabolism*; D015153:Blotting, Western; D005434:Flow Cytometry; D016023:Integrins / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015539:Platelet Activation / Q000502:physiology*; D016608:Talin / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D016023:Integrins; D008565:Membrane Proteins; C521189:RIAM protein, mouse; D016608:Talin