Localization of BMP Receptors in Specific Plasma Membrane Microdomains

Endocytosis of growth factor receptors plays an important role in the activation, propagation and attenuation of signaling pathways. Its malfunctioning can cause several pathologies. BMPs are members of the TGF-? superfamily and are involved in the regulation of proliferation, differentiation, chemotaxis and apoptosis. BMP signaling is initiated at two types of transmembrane serine/threonine kinases, BRI and BRII. BMP receptor activation occurs upon ligand binding to preformed complexes (PFCs) or BMP2-induced signaling complexes (BISCs) composed of BRI and BRII. Binding of BMP2 to PFCs results in activation of the Smad pathway, whereas BISCs initiate the activation of Smad-independent pathways via p38 resulting in the induction of Alkaline phosphatase (ALP). In this book, the localization of BMP receptors in distinct membrane domains and the consequential impact on BMP signaling are described. These findings propose an important regulatory impact of different endocytic routes and membrane regions on BMP signaling as well as that a distinct membrane localization of BMP receptors account for specific signaling properties initiated at PFCs or BISCs.