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The Journal of Neuroscience, November 28, 2007, 27(48):13098-13107; doi:10.1523/JNEUROSCI.3986-07.2007

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Cellular/Molecular
Polarity-Regulating Kinase Partitioning-Defective 1/Microtubule Affinity-Regulating Kinase 2 Negatively Regulates Development of Dendrites on Hippocampal Neurons

Takeshi Terabayashi,1 Tomohiko J. Itoh,2 Hideki Yamaguchi,3 Yuta Yoshimura,1 Yosuke Funato,1 Shigeo Ohno,4 and Hiroaki Miki1

1Laboratory of Intracellular Signaling, Institute for Protein Research, Osaka University, Suita, Osaka 565-0871, Japan, 2Division of Biological Sciences, Graduate School of Science, Nagoya University, Chikusa-ku, Nagoya 464-8602, Japan, 3Laboratory of Genome and Biosignal, Tokyo University of Pharmacy and Life Science, Hachioji, Tokyo 192-0392, Japan, and 4Department of Molecular Biology, Yokohama City University School of Medicine, Kanazawa-ku, Yokohama 236-0004, Japan

Correspondence should be addressed to Hiroaki Miki, Laboratory of Intracellular Signaling, Institute for Protein Research, Osaka University, 3-2 Yamadaoka, Suita, Osaka 565-0871, Japan. Email: hmiki{at}protein.osaka-u.ac.jp

Neurons are highly polarized cells that possess two morphologically and functionally different types of protrusions, axons and dendrites, that function in the transmission and reception of neural signals, respectively. A great deal of attention has been paid to the specification and guidance of axons, but the mechanism of dendrite development remains mostly unknown. We report here that a polarity-regulating kinase, partitioning-defective 1 (Par1b)/microtubule affinity-regulating kinase 2 (MARK2), specifically regulates development of dendrites in hippocampal neurons. Ectopic expression of Par1b/MARK2 shortens the length and decreases branching of dendrites without significant effects on axons. Knockdown of endogenous Par1b/MARK2 by RNA interference stimulates dendrite development. Wnt stimulation and Dishevelled expression, both of which are known to induce dendrite development, induced recruitment of Par1b/MARK2 to the membrane fraction. Expression of a Par1b/MARK2 mutant, that contains a myristoylation signal and accumulates exclusively in membranes, does not affect dendrite development. In addition, Par1b/MARK2 efficiently phosphorylated MAP2, which is localized mainly in dendrites. These results indicate that Par1b/MARK2 negatively regulates dendrite development through phosphorylation of MAP2.

Key words: dendrite; Wnt; Par1b/MARK2; dishevelled; translocation; MAP2


Received Dec. 3, 2006; revised Oct. 11, 2007; accepted Oct. 11, 2007.

Correspondence should be addressed to Hiroaki Miki, Laboratory of Intracellular Signaling, Institute for Protein Research, Osaka University, 3-2 Yamadaoka, Suita, Osaka 565-0871, Japan. Email: hmiki{at}protein.osaka-u.ac.jp




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