ActRIIA and BMPRII Type II BMP receptor subunits selectively required for Smad4-independent BMP7-evoked chemotaxis.
Bone morphogenetic protein (BMP)-evoked reorientation and chemotaxis of cells occurs with rapid onset and involves events local to the cell membrane. The signaling pathways underlying these rapid processes likely diverge from those mediating classical transcriptional responses to BMPs but it remains unclear how BMP receptors are utilized to generate distinct intracellular mechanisms. We show that BMP7-evoked chemotaxis of monocytic cells depends on the activity of canonical type II BMP receptors. Although the three canonical type II BMP receptors are expressed in monocytic cells, inhibition of receptor subunit expression by RNAi reveals that ActRIIA and BMPRII, but not ActRIIB, are each essential for BMP7-evoked chemotaxis but not required individually for BMP-mediated induction. Furthermore, the chemotactic response to BMP7 does not involve canonical Smad4-dependent signaling but acts through PI3K-dependent signaling, illustrating selective activation of distinct intracellular events through differential engagement of receptors. We suggest a model of a BMP receptor complex in which the coordinated activity of ActRIIA and BMPRII receptor subunits selectively mediates the chemotactic response to BMP7.
Perron
Jeanette C
JC
Departments of Physiology, Columbia University, New York, New York, United States of America.
Dodd
Jane
J
D030301:Activin Receptors, Type II / Q000378:metabolism*; D000818:Animals; D055419:Bone Morphogenetic Protein 7 / Q000494:pharmacology*; D052006:Bone Morphogenetic Protein Receptors, Type II / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002633:Chemotaxis / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D055785:Gene Knockdown Techniques; D006801:Humans; D051379:Mice; D008954:Models, Biological; D009000:Monocytes / Q000166:cytology / Q000187:drug effects; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D021122:Protein Subunits / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering; D015398:Signal Transduction / Q000187:drug effects; D051901:Smad4 Protein / Q000378:metabolism
D055419:Bone Morphogenetic Protein 7; D021122:Protein Subunits; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D051901:Smad4 Protein; D019869:Phosphatidylinositol 3-Kinases; D030301:Activin Receptors, Type II; D052006:Bone Morphogenetic Protein Receptors, Type II; C425585:activin receptor type II-A; C425584:activin receptor type II-B