A1 Refereed original research article in a scientific journal

Microtubule Stabilization by Bone Morphogenetic Protein Receptor-Mediated Scaffolding of c-Jun N-Terminal Kinase Promotes Dendrite Formation




AuthorsPodkowa M, Zhao X, Chow CW, Coffey ET, Davis RJ, Attisano L

PublisherAMER SOC MICROBIOLOGY

Publication year2010

JournalMolecular and Cellular Biology

Journal name in sourceMOLECULAR AND CELLULAR BIOLOGY

Journal acronymMOL CELL BIOL

Number in series9

Volume30

Issue9

First page 2241

Last page2250

Number of pages10

ISSN0270-7306

DOIhttps://doi.org/10.1128/MCB.01166-09


Abstract

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.




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