The Caveolin Scaffolding Domain Modifies 2-Amino-3-hydroxy-5-methyl-4-isoxazole Propionate Receptor Binding Properties by Inhibiting Phospholipase A2 Activity

Activation of the enzyme phospholipase (PLA 2) has been proposed to be part of the molecular mechanism involved in the alteration of 2-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) glutamate receptor responsiveness during long term changes in synaptic plasticity (long term potentiation). This study assesses the effect of the caveolin-1 scaffolding domain (CSD) on the activity of the regulatory enzyme PLA2. Caveolin-1 is a 22-kDa cholesterol-binding membrane protein known to inhibit the activity of most of its interacting partners. Our results show that the calcium-dependent cytosolic form of PLA2 (cPLA2) and caveolin-1 co-localized in mouse primary hippocampal neuron cultures and that they were co-immunoprecipitated from mouse hippocampal homogenates. A peptide corresponding to the scaffolding domain of caveolin-1 (Cav-(82-101)) dramatically inhibited cPLA2 activity in purified hippocampal synaptoneurosomes. Activation of endogenous PLA2 activity with KCl or melittin increased the binding of [3H]AMPA to its receptor. This effect was almost completely abolished by the addition of the CSD peptide to these preparations. Moreover, we demonstrated that the inhibitory action of the CSD peptide on AMPA receptor binding properties is specific (because a scrambled version of this peptide failed to have any effect) and that it is mediated by an inhibition of PLA2 enzymatic activity (because the CSD peptide failed to have an effect in membrane preparations lacking endogenous PLA2 activity). These results raised the possibility that caveolin-1, via the inhibition of cPLA2 enzymatic activity, may interfere with synaptic facilitation and long term potentiation formation in the hippocampus. Activation of the enzyme phospholipase (PLA 2) has been proposed to be part of the molecular mechanism involved in the alteration of 2-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) glutamate receptor responsiveness during long term changes in synaptic plasticity (long term potentiation). This study assesses the effect of the caveolin-1 scaffolding domain (CSD) on the activity of the regulatory enzyme PLA2. Caveolin-1 is a 22-kDa cholesterol-binding membrane protein known to inhibit the activity of most of its interacting partners. Our results show that the calcium-dependent cytosolic form of PLA2 (cPLA2) and caveolin-1 co-localized in mouse primary hippocampal neuron cultures and that they were co-immunoprecipitated from mouse hippocampal homogenates. A peptide corresponding to the scaffolding domain of caveolin-1 (Cav-(82-101)) dramatically inhibited cPLA2 activity in purified hippocampal synaptoneurosomes. Activation of endogenous PLA2 activity with KCl or melittin increased the binding of [3H]AMPA to its receptor. This effect was almost completely abolished by the addition of the CSD peptide to these preparations. Moreover, we demonstrated that the inhibitory action of the CSD peptide on AMPA receptor binding properties is specific (because a scrambled version of this peptide failed to have any effect) and that it is mediated by an inhibition of PLA2 enzymatic activity (because the CSD peptide failed to have an effect in membrane preparations lacking endogenous PLA2 activity). These results raised the possibility that caveolin-1, via the inhibition of cPLA2 enzymatic activity, may interfere with synaptic facilitation and long term potentiation formation in the hippocampus. Phospholipase (PLA2) 1The abbreviations used are: PLA2, phospholipase A2; AA, arachidonic acid; LTP, long term potentiation; AMPA, 2-amino-3-hydroxy-5-methyl-4-isoxazole propionate; CSD, caveolin scaffolding domain; cPLA2, cytosolic form of PLA2; GluR2, glutamate receptor subunit 2; CSD-X, scrambled version of the caveolin-1 peptide; AACOCF3, arachidonyl trifluoromethyl ketone. belongs to a superfamily of enzymes that play a central role in the regulation of arachidonic acid (AA) release from membrane phospholipids and catalyze the production of various metabolites. PLA2 activity has been postulated to play an important role in key metabolic pathways. In addition to its involvement in signal transduction, membrane repair, neurodegeneration, and apoptosis (1.Farooqui A.A. Yang H.C. Rosenberger T.A. Horrocks L.A. J. Neurochem. 1997; 69: 889-901Crossref PubMed Scopus (302) Google Scholar), there is a growing body of evidence suggesting a role in the modulation of neurotransmitter release and long term potentiation (LTP) (2.Dumuis A. Sebben M. Haynes L. Pin J.P. Bockaert J. Nature. 1988; 336: 68-70Crossref PubMed Scopus (503) Google Scholar, 3.Dumuis A. Sebben M. Fagni L. Prezeau L. Manzoni O. Cragoe Jr., E.J. Bockaert J. Mol. Pharmacol. 1993; 43: 976-981PubMed Google Scholar, 4.Lynch M.A. Errington M.L. Bliss T.V. Neuroscience. 1989; 30: 693-701Crossref PubMed Scopus (145) Google Scholar). Changes in synaptic function observed with LTP are thought to be the result of modifications of postsynaptic currents mediated by the 2-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) subtype of glutamate receptors (5.Davies S.N. Lester R.A. Reymann K.G. Collingridge G.L. Nature. 1989; 338: 500-503Crossref PubMed Scopus (365) Google Scholar, 6.Kauer J.A. Malenka R.C. Nicoll R.A. Neuron. 1988; 1: 911-917Abstract Full Text PDF PubMed Scopus (402) Google Scholar). PLA2 activity was shown to be part of the molecular mechanisms regulating AMPA receptor function during long term changes in synaptic operation (7.Chabot C. Bernard J. Normandin M. Ohayon M. Baudry M. Massicotte G. Brain Res. Dev. Brain Res. 1996; 93: 70-75Crossref PubMed Scopus (8) Google Scholar, 8.Bernard J. Chabot C. Gagne J. Baudry M. Massicotte G. Brain Res. 1995; 671: 195-200Crossref PubMed Scopus (15) Google Scholar, 9.Chabot C. Gagne J. Giguere C. Bernard J. Baudry M. Massicotte G. Hippocampus. 1998; 8: 299-309Crossref PubMed Scopus (43) Google Scholar). It has been proposed that during high frequency stimulation a large entry of calcium mediated by N-methyl-d-aspartate (NMDA) glutamate receptor activation might cause an increase in PLA2 activity. The enzyme would augment AMPA receptor affinity by changing the lipid environment of AMPA receptors, thereby producing LTP (10.Massicotte G. Cell Mol. Life Sci. 2000; 57: 1542-1550Crossref PubMed Scopus (38) Google Scholar). Recently, it has been reported that detergent-insoluble caveolin-rich membrane domains are markedly enriched in AMPA-type glutamate receptors (11.Suzuki T. Ito J. Takagi H. Saitoh F. Nawa H. Shimizu H. Brain Res. Mol. Brain Res. 2001; 89: 20-28Crossref PubMed Scopus (91) Google Scholar), AA and PLA2 (12.Pike L.J. Han X. Chung K.N. Gross R.W. Biochemistry. 2002; 41: 2075-2088Crossref PubMed Scopus (443) Google Scholar, 13.Murakami M. Kambe T. Shimbara S. Yamamoto S. Kuwata H. Kudo I. J. Biol. Chem. 1999; 274: 29927-29936Abstract Full Text Full Text PDF PubMed Scopus (157) Google Scholar), suggesting a possible role for PLA2 in caveolae-dependent cellular functions. Caveolae are small (50-100 nm) flask-shaped invaginations of the plasma membrane (14.Okamoto T. Schlegel A. Scherer P.E. Lisanti M.P. J. Biol. Chem. 1998; 273: 5419-5422Abstract Full Text Full Text PDF PubMed Scopus (1345) Google Scholar, 15.Severs N.J. J. Cell Sci. 1988; 90: 341-348Crossref PubMed Google Scholar). The main molecular features of caveolae are the presence of caveolin, an integral membrane protein (21-24 kDa) (16.Rothberg K.G. Heuser J.E. Donzell W.C. Ying Y.S. Glenney J.R. Anderson R.G. Cell. 1992; 68: 673-682Abstract Full Text PDF PubMed Scopus (1868) Google Scholar, 17.Kurzchalia T.V. Dupree P. Parton R.G. Kellner R. Virta H. Lehnert M. Simons K. J. Cell Biol. 1992; 118: 1003-1014Crossref PubMed Scopus (464) Google Scholar), and its distinct lipid composition (enrichment of cholesterol and glycosphingolipids) (18.Brown D.A. Rose J.K. Cell. 1992; 68: 533-544Abstract Full Text PDF PubMed Scopus (2610) Google Scholar, 19.Fiedler K. Kobayashi T. Kurzchalia T.V. Simons K. Biochemistry. 1993; 32: 6365-6373Crossref PubMed Scopus (225) Google Scholar). Three caveolin family members have recently been cloned and were designated caveolin-1, caveolin-2, and caveolin-3 (16.Rothberg K.G. Heuser J.E. Donzell W.C. Ying Y.S. Glenney J.R. Anderson R.G. Cell. 1992; 68: 673-682Abstract Full Text PDF PubMed Scopus (1868) Google Scholar, 20.Scherer P.E. Okamoto T. Chun M. Nishimoto I. Lodish H.F. Lisanti M.P. Proc. Natl. Acad. Sci. U. S. A. 1996; 93: 131-135Crossref PubMed Scopus (492) Google Scholar, 21.Tang Z. Scherer P.E. Okamoto T. Song K. Chu C. Kohtz D.S. Nishimoto I. Lodish H.F. Lisanti M.P. J. Biol. Chem. 1996; 271: 2255-2261Abstract Full Text Full Text PDF PubMed Scopus (610) Google Scholar). Caveolin-1 and -2 are ubiquitously expressed (22.Scherer P.E. Lisanti M.P. Baldini G. Sargiacomo M. Mastick C.C. Lodish H.F. J. Cell Biol. 1994; 127: 1233-1243Crossref PubMed Scopus (356) Google Scholar, 23.Scherer P.E. Lewis R.Y. Volonte D. Engelman J.A. Galbiati F. Couet J. Kohtz D.S. van Donselaar E. Peters P. Lisanti M.P. J. Biol. Chem. 1997; 272: 29337-29346Abstract Full Text Full Text PDF PubMed Scopus (472) Google Scholar) whereas caveolin-3 is almost exclusively found in muscles (21.Tang Z. Scherer P.E. Okamoto T. Song K. Chu C. Kohtz D.S. Nishimoto I. Lodish H.F. Lisanti M.P. J. Biol. Chem. 1996; 271: 2255-2261Abstract Full Text Full Text PDF PubMed Scopus (610) Google Scholar, 24.Parton R.G. Way M. Zorzi N. Stang E. J. Cell Biol. 1997; 136: 137-154Crossref PubMed Scopus (299) Google Scholar). Caveolae have been implicated in the sequestration of many signaling molecules (14.Okamoto T. Schlegel A. Scherer P.E. Lisanti M.P. J. Biol. Chem. 1998; 273: 5419-5422Abstract Full Text Full Text PDF PubMed Scopus (1345) Google Scholar). Caveolin is thought to function as a scaffolding protein within these membrane microdomains where it interacts with several signaling proteins (14.Okamoto T. Schlegel A. Scherer P.E. Lisanti M.P. J. Biol. Chem. 1998; 273: 5419-5422Abstract Full Text Full Text PDF PubMed Scopus (1345) Google Scholar, 25.Li S. Song K.S. Koh S.S. Kikuchi A. Lisanti M.P. J. Biol. Chem. 1996; 271: 28647-28654Abstract Full Text Full Text PDF PubMed Scopus (125) Google Scholar, 26.Gratton J.P. Fontana J. O'Connor D.S. Garcia-Cardena G. McCabe T.J. Sessa W.C. J. Biol. Chem. 2000; 275: 22268-22272Abstract Full Text Full Text PDF PubMed Scopus (274) Google Scholar). A short (20.Scherer P.E. Okamoto T. Chun M. Nishimoto I. Lodish H.F. Lisanti M.P. Proc. Natl. Acad. Sci. U. S. A. 1996; 93: 131-135Crossref PubMed Scopus (492) Google Scholar amino acids residues 82-101) cytosolic N-terminal region of caveolin, termed the caveolin scaffolding domain (CSD), is involved in the formation of caveolin oligomers and mediates the interaction with signaling molecules, which generally results in the inactivation of signaling (27.Lisanti M.P. Scherer P.E. Vidugiriene J. Tang Z. Hermanowski-Vosatka A. Tu Y.H. Cook R.F. Sargiacomo M. J. Cell Biol. 1994; 126: 111-126Crossref PubMed Scopus (815) Google Scholar). Most caveolin-interacting proteins identified so far contain a caveolin-binding motif located within their enzymatically active catalytic domain (28.Smart E.J. Graf G.A. McNiven M.A. Sessa W.C. Engelman J.A. Scherer P.E. Okamoto T. Lisanti M.P. Mol. Cell. Biol. 1999; 19: 7289-7304Crossref PubMed Scopus (924) Google Scholar). This caveolin-binding motif is also present within the catalytic domain of the cytosolic form of PLA2 (cPLA2); yet, virtually nothing is known about the potential relationship of caveolin with cPLA2. In this article, we report evidence demonstrating the presence of the cytosolic (85-kDa) PLA2 in caveolin-enriched membrane fractions isolated from hippocampal preparations. We also show that a CSD peptide can regulate the enzymatic activity of cPLA2 in these preparations. Finally, we explored the effect of the CSD fragment on PLA2-mediated modulation of AMPA receptor binding properties. Animals, Reagents, and Antibodies—Adult male, 3-month-old CD-1 mice were obtained from Charles River (St-Constant, Quebec, Canada). The anti-caveolin-1 polyclonal antibody (pAb N-20) was purchased from Santa Cruz Biotechnology (Santa Cruz, CA). The anti-mouse cPLA2 polyclonal antibody was from Oxford Biomedical Research (Oxford, MI), and the monoclonal anti-glutamate receptor (GluR2) antibody was from Chemicon International Inc. (Temecula, CA). Goat anti-rabbit and sheep anti-mouse biotinylated antibodies were from Calbiochem (San Diego, CA). Texas Red dye-conjugated donkey anti-rabbit IgG and fluorescein isothiocyanate-conjugated donkey anti-mouse IgG were purchased from Jackson ImmunoResearch Laboratories (West Cell were purchased from corresponding to amino acids of the scaffolding domain of caveolin-1 were and by high and by the M. Biotechnology of A scrambled version of the caveolin-1 peptide was also used as a cPLA2 was obtained from L. Research of trifluoromethyl and protein were purchased from and [3H]AMPA were obtained from were in with the for and of and were by the of of fractions were by with a as K.S. Scherer P.E. Tang Z. Okamoto T. S. M. Chu C. Kohtz D.S. Lisanti M.P. J. Biol. Chem. 1996; 271: Full Text Full Text PDF PubMed Scopus (610) Google Scholar). from mice were in a and The of protein in was to by of and the of a A was the by and of and in for fractions were the of of was used to proteins and by The protein of was a protein were to the of J. PubMed Google Scholar). mice were and the were and in with a of The was small and with a in The was and for The was in and for The was and used for binding PLA2 activity or of were with a in and The was for and for and the protein in was used for the Cell were with protein for were with of caveolin-1 or cPLA2 antibodies for Cell were with protein for were with were from by and to and were by and to for on were with polyclonal or anti-caveolin-1 antibodies in with with anti-rabbit biotinylated antibody in in were via the and to for Cell hippocampal cultures were from CD-1 as for K. P. Neuroscience. 1992; PubMed Scopus Google Scholar). were and the was and in The was with for and several in and were the was to and with The were used for were in and in for The were and in and for of with specific the were and with fluorescein isothiocyanate-conjugated donkey anti-mouse IgG for monoclonal antibody and Texas Red dye-conjugated donkey anti-rabbit IgG for anti-caveolin-1 and polyclonal of phospholipase activity acid was as by M.A. T. A. J. Neurochem. 1994; PubMed Scopus Google Scholar). were for in a and were and in of with or for and were The were and to were in [3H]AMPA activity of Life binding were as by Massicotte G. M. G. Baudry M. Mol. Pharmacol. Google Scholar). were in the presence or of of the CSD peptide 82-101) or for melittin or KCl were and were for were with a and [3H]AMPA was in a The binding was as that in the presence of a on the preparations were and the were The were in a and to were in in and with from hippocampal were by a that was shown to fractions K.S. Scherer P.E. Tang Z. Okamoto T. S. M. Chu C. Kohtz D.S. Lisanti M.P. J. Biol. Chem. 1996; 271: Full Text Full Text PDF PubMed Scopus (610) Google Scholar). shown in almost the expressed caveolin-1 is in the caveolae fractions and the most of the cellular protein is in the fractions a of the endogenous cPLA2 protein the molecular of R.A. J. Biol. Chem. 1988; Full Text PDF PubMed Google was in caveolae fractions demonstrating the presence of the cPLA2 protein in caveolin-enriched fractions from mice caveolin-1 a with cPLA2, hippocampal were to antibodies the N-terminal domain of caveolin-1 or cPLA2 The were by and to with antibodies caveolin-1 or cPLA2. shown in caveolin-1 protein was found in of cPLA2, a small of cPLA2 protein was in of these the of cPLA2 and caveolin-1 in hippocampal was cPLA2 and caveolin-1 were located the proteins to the and in many high of were also enriched on These results an cPLA2 and of by the CSD has been shown to the activity of several signaling molecules (27.Lisanti M.P. Scherer P.E. Vidugiriene J. Tang Z. Hermanowski-Vosatka A. Tu Y.H. Cook R.F. Sargiacomo M. J. Cell Biol. 1994; 126: 111-126Crossref PubMed Scopus (815) Google Scholar). This with the results to the possible of cPLA2 activity in with the CSD obtained by and of are a of synaptic plasma that with postsynaptic The presence of caveolin-1 and cPLA2 has been by on hippocampal preparations of for in the presence of in a lipid of AA of and a release corresponding to of CSD peptide a inhibition of release on PLA2 stimulation by melittin A effect of CSD peptide was observed with a of release with A was with a of of the purified CSD that the inhibition of AA release observed is the effect of the CSD peptide was on with the cPLA2 that the CSD peptide completely its effect on release of AA in the presence of the cPLA2 the cPLA2 as a of the CSD we also the inhibitory action of the CSD peptide on cPLA2 activity. shown in the CSD peptide completely abolished the effect of cPLA2 on AA whereas the failed to show any effect on cPLA2 activity. of the of AMPA by the CSD several that calcium-dependent PLA2 in changes in AMPA receptor properties G. M. G. Baudry M. Mol. Pharmacol. Google Scholar, G. P. G. Baudry M. Proc. Natl. Acad. Sci. U. S. A. PubMed Scopus Google Scholar), the results to the possibility that the inhibition of cPLA2 activity interfere with AMPA receptor was used to caveolin-1 and AMPA receptors are co-localized the cellular of hippocampal with a mouse monoclonal antibody the subunit of glutamate AMPA receptor and a polyclonal antibody that the body and as to of cellular caveolin-1 a on the a of and caveolin-1 in hippocampal It has been shown that of increased [3H]AMPA binding to membrane fractions J. A. Baudry M. Massicotte G. Brain Res. 1993; PubMed Scopus Google Scholar, J. Massicotte G. Baudry M. J. Neurochem. 1992; PubMed Scopus Google Scholar). It has also been reported that of with a of endogenous [3H]AMPA binding J. Chabot C. Gagne J. Baudry M. Massicotte G. Brain Res. 1995; 671: 195-200Crossref PubMed Scopus (15) Google Scholar). the effect of melittin and KCl in the presence of of CSD of with CSD peptide a of the and increase in [3H]AMPA binding to membrane the peptide the nm) AMPA binding in shown in the CSD peptide also the [3H]AMPA binding to its receptor. the possibility that the CSD peptide interacts with AMPA receptors, [3H]AMPA binding was on purified contain PLA2 activity preparations were obtained by a of hippocampal by of the Our results of AMPA receptor binding in these membrane preparations the inhibitory effect of CSD peptide was completely abolished the binding with were of In these phospholipase activity is that the CSD peptide modulation of [3H]AMPA binding on an inhibition of PLA2 enzymatic activity by the peptide a action of the on AMPA In the present we the presence of caveolin-1 and cPLA2 in mouse hippocampal Moreover, that a of cPLA2 is found in caveolin-rich membrane microdomains from hippocampal preparations. also that caveolin-1 and cPLA2 with suggesting that caveolin-1 may interfere with cPLA2 enzymatic activity. In of this we found that the peptide corresponding to the CSD peptide dramatically inhibited release of arachidonic In we that the inhibition of cPLA2 activity by the CSD peptide [3H]AMPA binding in synaptoneurosomes. these results that the inhibition of cPLA2 by caveolin-1 may be an important and mechanism for AMPA receptor binding properties. Caveolin-1 is an integral membrane and of its proposed is to regulate the activity of signaling proteins that in signaling molecules as and (28.Smart E.J. Graf G.A. McNiven M.A. Sessa W.C. Engelman J.A. Scherer P.E. Okamoto T. Lisanti M.P. Mol. Cell. Biol. 1999; 19: 7289-7304Crossref PubMed Scopus (924) Google Scholar) have been shown to be with It was recently reported that caveolae are enriched in AA (12.Pike L.J. Han X. Chung K.N. Gross R.W. Biochemistry. 2002; 41: 2075-2088Crossref PubMed Scopus (443) Google Scholar), the release of which is by PLA2. are of PLA2, cPLA2 and M. Kuwata H. Kudo I. 2000; PubMed Scopus Google Scholar). there are a of of PLA2 in the the cPLA2 is it AA from phospholipids J. Cell 1995; PubMed Scopus Google Scholar). In cPLA2 is to the in to in cytosolic the enzyme to the plasma membrane and the J. Biol. Chem. 1995; Full Text Full Text PDF PubMed Scopus Google Scholar). on cPLA2 to in in the of this Moreover, a interaction caveolin-1 and cPLA2, that caveolin-1 and cPLA2 proteins with In this the large of proteins known to with caveolin-1 might the small of caveolin-1 in cPLA2 the proteins that with caveolin-1, a to be the presence of a motif that interacts with the scaffolding domain of caveolin-1 (CSD) acids which is a region in caveolin-1 In a peptide from the scaffolding domain of caveolin-1 was used to the relationship caveolin-1 and the activity of the regulatory enzyme cPLA2. which are with are to study mechanisms of regulation of receptors and pathways. We found that the CSD peptide dramatically AA release from preparations. is a of endogenous the of the cPLA2 AACOCF3, we that the of AA release is The of any CSD peptide effect on with the cPLA2 and the inhibition of the cPLA2 activity by the CSD peptide identified cPLA2 as a of the CSD Moreover, the scrambled version of the CSD peptide AA the of the observed effect of the CSD fragment on endogenous cPLA2. It be that in of the are to be the This the CSD peptide we which is a can with cPLA2. might caveolin-1 inhibit the activity of possible mechanism for the CSD inhibition of cPLA2 activity is the enzyme cPLA2 to the membrane J. Biol. Chem. 1995; Full Text Full Text PDF PubMed Scopus Google Scholar) may its interaction with is that cPLA2 with signaling molecules caveolae may cPLA2 activity. cPLA2 can be by protein as protein A.A. Horrocks L.A. J. Res. 1994; PubMed Scopus Google Scholar) and protein M. A. Cell. 1993; Full Text PDF PubMed Scopus Google Scholar), which are known to be inhibited by caveolin-1 N. Yamamoto M. C. J. T. S. Couet J. Lisanti M.P. J. Biol. Chem. 1997; 272: Full Text Full Text PDF PubMed Scopus Google Scholar). the mechanism for the inhibition of cPLA2 activity by caveolin-1 is the effect observed may have an important role in it has recently that activation of the calcium-dependent PLA2 be part of the molecular mechanisms involved in of AMPA receptor properties during long term changes in synaptic operation (LTP) (7.Chabot C. Bernard J. Normandin M. Ohayon M. Baudry M. Massicotte G. Brain Res. Dev. Brain Res. 1996; 93: 70-75Crossref PubMed Scopus (8) Google Scholar, 8.Bernard J. Chabot C. Gagne J. Baudry M. Massicotte G. Brain Res. 1995; 671: 195-200Crossref PubMed Scopus (15) Google Scholar, 9.Chabot C. Gagne J. Giguere C. Bernard J. Baudry M. Massicotte G. Hippocampus. 1998; 8: 299-309Crossref PubMed Scopus (43) Google Scholar). 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It is that a small of the effect of CSD peptide on AMPA binding might have been mediated by the inhibition of the cPLA2. as we with the cPLA2 the effect of melittin on is This that the inhibition of the cPLA2 of the enzyme might be involved in the of AMPA which is with the and inhibition of the purified cPLA2 by the CSD We also demonstrated that the inhibitory action of the CSD peptide on AMPA binding on its modulation of PLA2 activity by in where PLA2 enzymatic activity is evidence has shown that [3H]AMPA binding is LTP S. G. S. Baudry M. R.F. Proc. Natl. Acad. Sci. U. S. A. 1993; 90: PubMed Scopus Google Scholar, A. R. Nature. 1998; PubMed Scopus Google Scholar, J. A. Massicotte G. Hippocampus. 1994; PubMed Scopus Google Scholar). Moreover, several that that inhibit PLA2 activity interfere with LTP M.A. Errington M.L. Bliss T.V. Neuroscience. 1989; 30: 693-701Crossref PubMed Scopus (145) Google Scholar, Bliss T.V. 1989; PubMed Scopus Google Scholar, G. G. Baudry M. Brain Res. PubMed Scopus Google Scholar). we that an of caveolin-1 in the as that in Yamamoto M. C. S. Mol. Cell. 2001; PubMed Scopus Google Scholar, J. Biol. Chem. 2000; 275: Full Text Full Text PDF PubMed Scopus Google Scholar, S. and J. Scholar) or in S. and J. Scholar), might interfere with synaptic In we show for the the regulation of cPLA2 activity and the modulation of AMPA receptor binding properties by the scaffolding domain of These results the possibility that caveolin-1 may interfere with synaptic and LTP In this this to the potential involvement of the caveolin scaffolding domain in regulating changes of AMPA receptor properties in synaptic plasticity and LTP formation in We L. Research of for cPLA2. We also for of this and for

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