Microtubule Stabilization by Bone Morphogenetic Protein Receptor-Mediated Scaffolding of c-Jun N-Terminal Kinase Promotes Dendrite Formation
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.
- University of Massachusetts Medical School United States
- University of Toronto Canada
- Albert Einstein College of Medicine United States
- Åbo Akademi University Finland
- Turku Centre for Biotechnology Finland
Bone Morphogenetic Protein 7, Organogenesis, JNK Mitogen-Activated Protein Kinases, Cell Biology, Dendrites, Bone Morphogenetic Protein Receptors, Type II, Biochemistry, Microtubules, Protein Structure, Tertiary, Cellular and Molecular Physiology, Enzyme Activation, Mice, Cell Line, Tumor, Animals, Cell Surface Extensions, Molecular Biology, Microtubule-Associated Proteins, Protein Binding
Bone Morphogenetic Protein 7, Organogenesis, JNK Mitogen-Activated Protein Kinases, Cell Biology, Dendrites, Bone Morphogenetic Protein Receptors, Type II, Biochemistry, Microtubules, Protein Structure, Tertiary, Cellular and Molecular Physiology, Enzyme Activation, Mice, Cell Line, Tumor, Animals, Cell Surface Extensions, Molecular Biology, Microtubule-Associated Proteins, Protein Binding
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