A proposed model of Sema4D exodomain shedding regulated by the interaction of calmodulin with the Sema4D cytoplasmic domain. Sema4D was shown to be a calmodulin-binding protein with a site of interaction in the membrane-proximal cytoplasmic domain that regulates the cleavage of the membrane-proximal exodomain of Sema4D by ADAM17. It was proposed that releasing the association of calmodulin with Sema4D by incubation with a peptide CBPS or a calmodulin inhibitor W7 induces the conformational change that favors to the accessibility of its sheddases, mediating Sema4D shedding. This peptide also induces cleavage of GPVI and GPIbα, implying a generality of this mechanism that calmodulin regulates shedding of platelet membrane receptors regardless of what their sheddases are.