Figure 8. Model of differential receptor subunit recruitment and signaling underlying BMP-evoked chemotaxis and trophic actions.

We have demonstrated that ActRIIA and BMPRII receptor subunits are both selectively required for BMP7-evoked chemotaxis in monocytic cells. How do the individual receptor subunits contribute to this activity? Do they work together in a common complex? A,B: Our data support a model in which BMP7 engages both ActRIIA and BMPRII subunits either as part of a heteromeric type II receptor pair (A) or as homodimers, possibly forming unique receptor complexes combining pairs of each of the type II receptor subunits (B). The identity of the type I receptors that contribute to this complex is not known, although recent evidence implicates BMPRIB in BMP-dependent axon guidance [48], [49]. Engagement of ActRIIA and BMPRII subunits by chemotropic BMPs activates a signaling pathway leading to PI3K activity and cytoskeletal reorganization that is independent of Smad4-mediated nuclear signaling. C: In contrast, BMP6 does not stimulate chemotaxis, presumably being unable to recruit or activate the ActRIIA:BMPRII complex necessary for chemotropic signaling. In the same cell, however, BMP7 and BMP6 share the ability to activate Smad-dependent transcriptional pathways, through receptor mechanisms that do not depend selectively on either ActRIIA or BMPRII.