Fear conditioning is associated with altered integration of PLC and ERK signaling in the hippocampus.
The extracellular signal-regulated protein kinases (ERKs) are proline-directed, serine/threonine kinases that regulate a variety of cellular functions, including proliferation, differentiation, and plasticity. In the present report, we provide evidence that ERK2 and phosphatidylinositol-specific phospholipase C (PLC)-beta and -gamma isozymes interact in the rat hippocampal formation. We found that anti-PLC-beta1a, -beta2, -beta4, -gamma1 and -gamma2, but not -beta3, immune complexes isolated from rat hippocampal formation postnuclear fractions contain anti-ERK2 immunoreactivity. Further, we show that PLC catalytic activity is associated with anti-ERK2 immunoprecipitates isolated from the hippocampal formation, and that the amount of enzyme activity is significantly increased following fear-conditioned learning. The observed interactions may be mediated by consensus sequences conforming to an ERK2 docking site, termed a D-domain, that we identified in PLC-beta1a, -beta2, -beta4 -gamma1 and -gamma2. Based on these results, we propose that PLC-beta and PLC-gamma isozymes form signaling complexes with ERK2 in rat brain, and these complexes play critical roles in learning and memory, as well as a variety of other neuronal functions.
Buckley
Colin T
CT
Department of Neurosciences, MSC08 4740, University of New Mexico School of Medicine, 1 University of New Mexico, Albuquerque, NM 87131-0001, USA.
Caldwell
Kevin K
KK
D000818:Animals; D003213:Conditioning, Psychological / Q000502:physiology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000502:physiology*; D005239:Fear / Q000502:physiology*; D005260:Female; D006624:Hippocampus / Q000201:enzymology* / Q000502:physiology; D007527:Isoenzymes / Q000378:metabolism* / Q000502:physiology*; D020935:MAP Kinase Signaling System / Q000502:physiology*; D019950:Mitogen-Activated Protein Kinase 1 / Q000502:physiology*; D048052:Mitogen-Activated Protein Kinase 3 / Q000502:physiology*; D054799:Phospholipase C beta; D051966:Phospholipase C gamma; D051381:Rats; D017207:Rats, Sprague-Dawley; D010738:Type C Phospholipases / Q000378:metabolism* / Q000502:physiology*
D007527:Isoenzymes; D048049:Extracellular Signal-Regulated MAP Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D010738:Type C Phospholipases; D054799:Phospholipase C beta; C518038:Plcb2 protein, rat; C518041:Plcb3 protein, rat; C518044:Plcb4 protein, rat; D051966:Phospholipase C gamma