Implications for GPVI signaling. A model is shown for signaling by receptor clustering, in which clustering triggers a signaling cascade via the FcR γ-chain coreceptor. This would resemble TCR signaling via the related ζ-chain coreceptor, which occurs by clustering of at least 2 TCR complexes in an orientation-independent manner, with the proximity of the TCR complexes correlating to the strength of the signal.54 An individual GPVI dimer would not necessarily allow the γ-chains to approach closely enough to trigger signaling, due to the long GPVI stalk region. However, multiple GPVI molecules bound to a collagen fiber would juxtapose several γ-chains in a small volume, triggering activation. Although GPVI in the model is illustrated as a dimer, the proposed mechanism of GPVI clustering by fibrous collagen would also apply if GPVI were monomeric at the platelet surface.
