NMDA-glutamate receptors regulate phosphorylation of dendritic cytoskeletal proteins in the hippocampus.
Most forms of synaptic potentiation need the activation of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptors which generate changes in dendritic morphology of postsynaptic neurons. Since microtubule proteins have an essential role in dendritic morphology, they may be involved and regulated during the modifications of dendritic morphology associated with synaptic potentiation. The phosphorylation of the microtubule-associated proteins (MAPs) has been analyzed in situ after activation or blockade of NMDA-glutamate receptors in hippocampal slices. The phosphorylation of MAP1B and MAP2 has been studied by using several antibodies raised against phosphorylation-sensitive epitopes. Whereas antibodies 125 and 305 recognize phosphorylated epitopes on MAP1B and MAP2, respectively, Ab 842 recognizes a phosphorylatable sequence on MAP1B only when it is dephosphorylated. NMDA treatment decreased the phosphorylation state of the epitope recognized by the antibody 305 on MAP2 and caused a slight dephosphorylation of MAP1B sequences recognized by Ab 125 and 842. Moreover, exposure to APV (an antagonist of NMDA-glutamate receptors) counteracted the effect of NMDA and induced an increase in the phosphorylation state of these sequences in MAP2. Since phosphorylation regulates the interaction of MAPs with cytoskeleton, the results suggest that the modulation of the phosphorylated state of MAP2 by NMDA-glutamate receptors may be implicated in dendritic plasticity.
Sánchez
C
C
Centro de Biología Molecular, Universidad Autónoma de Madrid, Cantoblanco, Spain.
Ulloa
L
L
Montoro
R J
RJ
López-Barneo
J
J
Avila
J
J
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D003712:Dendrites / Q000187:drug effects / Q000378:metabolism*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008297:Male; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009473:Neuronal Plasticity / Q000187:drug effects; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000502:physiology*
D003598:Cytoskeletal Proteins; D018691:Excitatory Amino Acid Antagonists; D008869:Microtubule-Associated Proteins; D016194:Receptors, N-Methyl-D-Aspartate; D015763:2-Amino-5-phosphonovalerate