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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

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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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