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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

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

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 component of cross-bridges between microtubules in dendrites, and is known to stabilize microtubules. MAP2 also has a binding domain for the regulatory subunit II of cAMP-dependent protein kinase (PKA). We found that there is reduction in microtubule density in dendrites and a reduction of dendritic length in MAP2-deficient mice. Moreover, there is a significant reduction of various subunits of PKA in dendrites and total amounts of various PKA subunits in hippocampal tissue and cultured neurons. In MAP2-deficient cultured neurons, the induction rate of phosphorylated CREB after forskolin stimulation was much lower than in wild-type neurons. Therefore, MAP2 is an anchoring protein of PKA in dendrites, whose loss leads to reduced amount of dendritic and total PKA and reduced activation of CREB.

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

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