Microtubule stabilization by bone morphogenetic protein receptor-mediated scaffolding of c-Jun N-terminal kinase promotes dendrite formation.
Neuronal outgrowth occurs via coordinated remodeling of the cytoskeleton involving both actin and microtubules. Microtubule stabilization drives the extending neurite, yet little is known of the molecular mechanisms whereby extracellular cues regulate microtubule dynamics. Bone morphogenetic proteins (BMPs) play an important role in neuronal differentiation and morphogenesis, and BMP7 in particular induces the formation of dendrites. Here, we show that BMP7 induces stabilization of microtubules in both a MAP2-dependent neuronal cell culture model and in dendrites of primary cortical neurons. BMP7 rapidly activates c-Jun N-terminal kinases (JNKs), known regulators of microtubule dynamics, and we show that JNKs associate with the carboxy terminus of the BMP receptor, BMPRII. Activation and binding of JNKs to BMPRII is required for BMP7-induced microtubule stabilization and for BMP7-mediated dendrite formation in primary cortical neurons. These data indicate that BMPRII acts as a scaffold to localize and coordinate cytoskeletal remodeling and thereby provides an efficient means for extracellular cues, such as BMPs, to control neuronal dendritogenesis.
Podkowa
Monika
M
Department of Biochemistry and Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario M5S 3E1, Canada.
Zhao
Xin
X
Chow
Chi-Wing
CW
Coffey
Eleanor T
ET
Davis
Roger J
RJ
Attisano
Liliana
L
D000818:Animals; D055419:Bone Morphogenetic Protein 7 / Q000494:pharmacology; D052006:Bone Morphogenetic Protein Receptors, Type II / Q000378:metabolism*; D045744:Cell Line, Tumor; D022081:Cell Surface Extensions / Q000187:drug effects / Q000201:enzymology; D003712:Dendrites / Q000187:drug effects / Q000201:enzymology*; D004789:Enzyme Activation / Q000187:drug effects; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008870:Microtubules / Q000187:drug effects / Q000201:enzymology*; D038081:Organogenesis / Q000187:drug effects; D011485:Protein Binding / Q000187:drug effects; D017434:Protein Structure, Tertiary
D055419:Bone Morphogenetic Protein 7; D008869:Microtubule-Associated Proteins; C079240:Mtap2 protein, mouse; D048031:JNK Mitogen-Activated Protein Kinases; D052006:Bone Morphogenetic Protein Receptors, Type II