Yotiao protein, a ligand for the NMDA receptor, binds and targets cAMP-dependent protein kinase II(1).
A yeast two-hybrid screen revealed that regulatory subunits (RII) of PKAII bind the Yotiao protein. Yotiao interacts with the NR1 subunit of the NMDA receptor. A purified C-terminal fragment of Yotiao binds PKAII, via an RII binding site constituted by amino acid residues 1452-1469, with a dissociation constant (K(d)) between 50 and 90 nM in vitro. A stable complex composed of Yotiao, RII and NR1 was immunoprecipitated from whole rat brain extracts. Immunostaining analysis disclosed that Yotiao, RIIbeta and NR1 colocalize in striatal and cerebellar neurons. Co-assembly of Yotiao/PKAII complexes with NR1 subunits may promote cAMP-dependent modulation of NMDA receptor activity at synapses, thereby influencing brain development and synaptic plasticity.
Feliciello
A
A
Dipartimento di Biologia e Patologia Molecolare e Cellulare, Centro di Endocrinologia ed Oncologia Sperimentale CNR, Facoltá di Medicina, Universitá Federico II, 80131, Naples, Italy. feliciel@unina.it
Cardone
L
L
Garbi
C
C
Ginsberg
M D
MD
Varrone
S
S
Rubin
C S
CS
Avvedimento
E V
EV
Gottesman
M E
ME
D054758:A Kinase Anchor Proteins; D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000737:chemistry / Q000378:metabolism*; D008024:Ligands; D051379:Mice; D008969:Molecular Sequence Data; D011485:Protein Binding; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity
D054758:A Kinase Anchor Proteins; D048868:Adaptor Proteins, Signal Transducing; C486537:Akap9 protein, rat; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D008024:Ligands; D016194:Receptors, N-Methyl-D-Aspartate; D011994:Recombinant Proteins; D017868:Cyclic AMP-Dependent Protein Kinases