MAP2 is required for dendrite elongation, PKA anchoring in dendrites, and proper PKA signal transduction

doi:10.1083/jcb.200110134

Published 5 August 2002. doi:10.1083/jcb.200110134

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© The Rockefeller University Press, 0021-9525/2002/8/541 $5.00
The Journal of Cell Biology, Volume 158, Number 3, August 5, 2002 541-549

Article

MAP2 is required for dendrite elongation, PKA anchoring in dendrites, and proper PKA signal transduction

Akihiro Harada, Junlin Teng, Yosuke Takei, Keiko Oguchi and Nobutaka Hirokawa

Department of Cell Biology and Anatomy, Graduate School of Medicine, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo, 113-0033, Japan

Address correspondence to N. Hirokawa, Department of Cell Biology and Anatomy, Graduate School of Medicine, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033, Japan. Tel: 81-3-5841-3326. Fax: 81-3-5802-8646. E-mail: hirokawa{at}m.u-tokyo.ac.jp

Microtubule-associated protein 2 (MAP2) is a major componentof cross-bridges between microtubules in dendrites, and is knownto stabilize microtubules. MAP2 also has a binding domain forthe regulatory subunit II of cAMP-dependent protein kinase (PKA).We found that there is reduction in microtubule density in dendritesand a reduction of dendritic length in MAP2-deficient mice.Moreover, there is a significant reduction of various subunitsof PKA in dendrites and total amounts of various PKA subunitsin hippocampal tissue and cultured neurons. In MAP2-deficientcultured neurons, the induction rate of phosphorylated CREBafter forskolin stimulation was much lower than in wild-typeneurons. Therefore, MAP2 is an anchoring protein of PKA in dendrites,whose loss leads to reduced amount of dendritic and total PKAand reduced activation of CREB.

Key Words: knockout; microtubule; cAMP-dependent protein kinase; regulatory subunit; CREB

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