MAP2 is required for dendrite elongation, PKA anchoring in dendrites, and proper PKA signal transduction.
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.
Harada
Akihiro
A
Department of Cell Biology and Anatomy, Graduate School of Medicine, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Japan.
Teng
Junlin
J
Takei
Yosuke
Y
Oguchi
Keiko
K
Hirokawa
Nobutaka
N
D000818:Animals; D002451:Cell Compartmentation / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics*; D048429:Cell Size / Q000235:genetics; D002478:Cells, Cultured; D002531:Cerebellum / Q000002:abnormalities / Q000473:pathology / Q000648:ultrastructure; D002540:Cerebral Cortex / Q000002:abnormalities / Q000473:pathology / Q000648:ultrastructure; D005576:Colforsin / Q000494:pharmacology; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D003712:Dendrites / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D015536:Down-Regulation / Q000235:genetics; D018390:Gene Targeting; D005822:Genetic Vectors; D006624:Hippocampus / Q000002:abnormalities* / Q000473:pathology / Q000648:ultrastructure; D007150:Immunohistochemistry; D051379:Mice; D018345:Mice, Knockout; D008854:Microscopy, Electron; D008869:Microtubule-Associated Proteins / Q000172:deficiency* / Q000235:genetics; D008870:Microtubules / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D010766:Phosphorylation; D011485:Protein Binding / Q000235:genetics; D017434:Protein Structure, Tertiary / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics*
D017362:Cyclic AMP Response Element-Binding Protein; D008869:Microtubule-Associated Proteins; D005576:Colforsin; D017868:Cyclic AMP-Dependent Protein Kinases