Activin induces long-lasting N-methyl-D-aspartate receptor activation via scaffolding PDZ protein activin receptor interacting protein 1.
Calcium entry into the postsynaptic neuron through N-methyl-D-aspartate-type glutamate receptors (NMDARs) triggers the induction of long-term potentiation (LTP), which is considered to contribute to synaptic plasticity and plays a critical role in behavioral learning. We report here that activin, a member of the transforming growth factor-beta (TGF-beta) superfamily, promotes phosphorylation of NMDARs and increases the Ca2+ influx through these receptors in primary cultured rat hippocampal neurons. This signal transduction occurs in a functional complex of activin receptors, NMDARs, and Src family tyrosine kinases, including Fyn, formed on a multimer of postsynaptic scaffolding postsynaptic density protein 95/Dlg/ZO-1 (PDZ), activin receptor interacting protein 1 (ARIP1). Activin-induced NMDAR activation persists for more than 24 h, which is complimentary to the activation time of NMDARs by brain-derived neurotrophic factor (BDNF). Our results suggest that activin is a unique and powerful potentiator for NMDAR-dependent signaling, which could be involved in the regulatory mechanisms of synaptic plasticity.
Kurisaki
A
A
Institute for Enzyme Research, The University of Tokushima, Kuramoto, Tokushima 770-8503, Japan. akikuri@hotmail.com
Inoue
I
I
Kurisaki
K
K
Yamakawa
N
N
Tsuchida
K
K
Sugino
H
H
D028341:Activins / Q000494:pharmacology*; D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D004149:Dioxoles / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004622:Embryo, Mammalian; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D018698:Glutamic Acid / Q000494:pharmacology; D051528:Guanylate Kinases; D006624:Hippocampus / Q000166:cytology; D047468:Immunoprecipitation; D009474:Neurons / Q000187:drug effects*; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D011506:Proteins / Q000502:physiology*; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D013997:Time Factors; D014162:Transfection
C459179:4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide; D048868:Adaptor Proteins, Signal Transducing; D001549:Benzamides; D004149:Dioxoles; D004791:Enzyme Inhibitors; D018691:Excitatory Amino Acid Antagonists; D011506:Proteins; D011810:Quinoxalines; D016194:Receptors, N-Methyl-D-Aspartate; D028341:Activins; D018698:Glutamic Acid; C056723:FG 9041; D016291:Dizocilpine Maleate; D051528:Guanylate Kinases; C405684:Magi2 protein, mouse; D010751:Phosphopyruvate Hydratase; D002118:Calcium