LTP but not seizure is associated with up-regulation of AKAP-150.
We have used differential display to profile and compare the mRNAs expressed in the hippocampus of freely moving animals after the induction of long-term potentiation (LTP) at the perforant path-dentate gyrus synapse with control rats receiving low-frequency stimulation. We have combined this with in situ hybridization and have identified A-kinase anchoring protein of 150 kDa (AKAP-150) as a gene selectively up-regulated during the maintenance phase of LTP. AKAP-150 mRNA has a biphasic modulation in the dentate gyrus following the induction of LTP. The expression of AKAP-150 was 29% lower than stimulated controls 1 h after the induction of LTP. Its expression was enhanced 3 (50%), 6 (239%) and 12 h (210%) after induction, returning to control levels by 24 h postinduction. The NMDA receptor antagonist CPP blocked the tetanus-induced modulation of AKAP-150 expression. Interestingly, strong generalized stimulation produced by electroconvulsive shock did not increase the expression of AKAP-150. This implies that the AKAP-150 harbours a novel property of selective responsiveness to the stimulation patterns that trigger NMDA-dependent LTP in vivo. Its selective up-regulation during LTP and its identified functions as a scaffold for protein kinase A, protein kinase C, calmodulin, calcineurin and ionotropic glutamate receptors suggest that AKAP-150 encodes is an important effector protein in the expression of late LTP.
Génin
A
A
Hôpital La Pitié Salpêtrière, UMR CNRS 9923, LGN, F-75013 Paris, France.
French
P
P
Doyère
V
V
Davis
S
S
Errington
M L
ML
Maroun
M
M
Stean
T
T
Truchet
B
B
Webber
M
M
Wills
T
T
Richter-Levin
G
G
Sanger
G
G
Hunt
S P
SP
Mallet
J
J
Laroche
S
S
Bliss
T V P
TV
O'Connor
V
V
D054758:A Kinase Anchor Proteins; D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D002352:Carrier Proteins / Q000378:metabolism*; D004558:Electric Stimulation; D004597:Electroshock; D006624:Hippocampus / Q000378:metabolism*; D017403:In Situ Hybridization; D017774:Long-Term Potentiation / Q000502:physiology*; D008297:Male; D009473:Neuronal Plasticity / Q000502:physiology; D010879:Piperazines / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism; D012640:Seizures / Q000378:metabolism; D015854:Up-Regulation
D054758:A Kinase Anchor Proteins; D048868:Adaptor Proteins, Signal Transducing; C415703:Akap5 protein, rat; D000927:Anticonvulsants; D002352:Carrier Proteins; D010879:Piperazines; D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate; C050592:3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid