TY - JOUR
T1 - Microtubule stabilization by bone morphogenetic protein receptor-mediated scaffolding of c-Jun n-Terminal kinase promotes dendrite formation
AU - Podkowa, Monika
AU - Zhao, Xin
AU - Chow, Chi Wing
AU - Coffey, Eleanor T.
AU - Davis, Roger J.
AU - Attisano, Liliana
N1 - Funding Information:
This research was partly supported by the ISARELI academy for science and the Technion foundation for the promotion of research. The generous support is gratefully acknowledged.
PY - 2010/5
Y1 - 2010/5
N2 - 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.
AB - 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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U2 - 10.1128/MCB.01166-09
DO - 10.1128/MCB.01166-09
M3 - Article
C2 - 20176805
AN - SCOPUS:77950674624
SN - 0270-7306
VL - 30
SP - 2241
EP - 2250
JO - Molecular and cellular biology
JF - Molecular and cellular biology
IS - 9
ER -