PKA is an integral part of neuronal class C L-type Ca2+ channels, and the A-kinase anchor protein MAP2B directly binds to the alpha1 subunit to mediate this interaction.
The study demonstrates that PKA is an integral part of neuronal class C L-type Ca2+ channels, mediated by the anchor protein MAP2B, which may facilitate rapid phosphorylation upon cAMP signaling.
Phosphorylation by cAMP-dependent protein kinase (PKA) increases the activity of class C L-type Ca2+ channels which are clustered at postsynaptic sites and are important regulators of neuronal functions. We investigated a possible mechanism that could ensure rapid and efficient phosphorylation of these channels by PKA upon stimulation of cAMP-mediated signaling pathways. A kinase anchor proteins (AKAPs) bind to the regulatory R subunits of PKA and target the holoenzyme to defined subcellular compartments and substrates. Class C channels isolated from rat brain extracts by immunoprecipitation contain an endogenous kinase that phosphorylates kemptide, a classic PKA substrate peptide, and also the main phosphorylation site for PKA in the pore-forming α1 subunit of the class C channel complex, serine 1928. The kinase activity is inhibited by the PKA inhibitory peptide PKI(5–24) and stimulated by cAMP. Physical association of the catalytic C subunit of PKA with the immunoisolated class C channel complex was confirmed by immunoblotting. A direct protein overlay binding assay performed with 32P-labeled RIIβ revealed a prominent AKAP with an M r of 280,000 in class C channel complexes. The protein was identified by immunoblotting as the microtubule-associated protein MAP2B, a well established AKAP. Class C channels did not contain tubulin and MAP2B association was not disrupted by dilution or addition of nocodazole, two treatments that cause dissociation of microtubules. In vitro experiments show that MAP2B can directly bind to the α1 subunit of the class C channel. Our findings indicate that PKA is an integral part of neuronal class C L-type Ca2+ channels and suggest that the AKAP MAP2B may mediate this interaction. Neither PKA nor MAP2B were detected in immunoprecipitates of α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid-type glutamate receptors or class B N-type Ca2+ channels. Accordingly, MAP2B docked at class C Ca2+ channels may be important for recruiting PKA to postsynaptic sites. Phosphorylation by cAMP-dependent protein kinase (PKA) increases the activity of class C L-type Ca2+ channels which are clustered at postsynaptic sites and are important regulators of neuronal functions. We investigated a possible mechanism that could ensure rapid and efficient phosphorylation of these channels by PKA upon stimulation of cAMP-mediated signaling pathways. A kinase anchor proteins (AKAPs) bind to the regulatory R subunits of PKA and target the holoenzyme to defined subcellular compartments and substrates. Class C channels isolated from rat brain extracts by immunoprecipitation contain an endogenous kinase that phosphorylates kemptide, a classic PKA substrate peptide, and also the main phosphorylation site for PKA in the pore-forming α1 subunit of the class C channel complex, serine 1928. The kinase activity is inhibited by the PKA inhibitory peptide PKI(5–24) and stimulated by cAMP. Physical association of the catalytic C subunit of PKA with the immunoisolated class C channel complex was confirmed by immunoblotting. A direct protein overlay binding assay performed with 32P-labeled RIIβ revealed a prominent AKAP with an M r of 280,000 in class C channel complexes. The protein was identified by immunoblotting as the microtubule-associated protein MAP2B, a well established AKAP. Class C channels did not contain tubulin and MAP2B association was not disrupted by dilution or addition of nocodazole, two treatments that cause dissociation of microtubules. In vitro experiments show that MAP2B can directly bind to the α1 subunit of the class C channel. Our findings indicate that PKA is an integral part of neuronal class C L-type Ca2+ channels and suggest that the AKAP MAP2B may mediate this interaction. Neither PKA nor MAP2B were detected in immunoprecipitates of α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid-type glutamate receptors or class B N-type Ca2+ channels. Accordingly, MAP2B docked at class C Ca2+ channels may be important for recruiting PKA to postsynaptic sites. cAMP-dependent protein kinase protein kinase A anchor protein α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid microtubule-associated protein polyacrylamide gel electrophoresis protein kinase C Ca2+ influx through voltage-gated L-type Ca2+ channels controls a variety of neuronal functions including synaptic plasticity, membrane excitability, and gene expression (1Grover L.M. Teyler T.J. Nature. 1990; 347: 477-479Crossref PubMed Scopus (595) Google Scholar, 2Bolshakov V.Y. Siegelbaum S.A. Science. 1994; 264: 148-152Crossref Scopus (413) Google Scholar, 3Christie B.R. Schexnayder L.K. Johnston D. J. Neurophys. 1997; 77: 1651-1655Crossref PubMed Scopus (70) Google Scholar, 4Marrion N.V. Tavalin S.T. Nature. 1998; 395: 900-905Crossref PubMed Scopus (464) Google Scholar, 5Ghosh A. Greenberg M.E. Science. 1995; 268: 239-247Crossref PubMed Scopus (1247) Google Scholar). Like other voltage-gated Ca2+ channels, neuronal L-type channels consist of several subunits including the α1, α2δ, and β polypeptides (6Catterall W.A. Annu. Rev. Biochem. 1995; 64: 493-531Crossref PubMed Scopus (781) Google Scholar). α1 is the critical subunit which constitutes the ion-conducting pore (6Catterall W.A. Annu. Rev. Biochem. 1995; 64: 493-531Crossref PubMed Scopus (781) Google Scholar). Most if not all neuronal L-type channels in the brain are formed from either α1C or α1D(7Hell J.W. Westenbroek R.E. Warner C. Ahlijanian M.K. Prystay W. Gilbert M.M. Snutch T.P. Catterall W.A. J. Cell Biol. 1993; 123: 949-962Crossref PubMed Scopus (648) Google Scholar). Two sizes of α1C and α1D polypeptides are evident in situ (7Hell J.W. Westenbroek R.E. Warner C. Ahlijanian M.K. Prystay W. Gilbert M.M. Snutch T.P. Catterall W.A. J. Cell Biol. 1993; 123: 949-962Crossref PubMed Scopus (648) Google Scholar). The shorter forms (180–190 kDa) are derived from their longer counterparts (200–220 kDa) by C-terminal truncation (8Hell J.W. Yokoyama C.T. Wong S.T. Warner C. Snutch T.P. Catterall W.A. J. Biol. Chem. 1993; 268: 19451-19457Abstract Full Text PDF PubMed Google Scholar, 9Hell J.W. Westenbroek R.E. Elliott E.M. Catterall W.A. Ann. N. Y. Acad. Sci. 1994; 747: 282-293Crossref PubMed Scopus (30) Google Scholar). In hippocampal slices, this modification of the C terminus of α1C is induced by Ca2+ influx through N-methyl-d-aspartate receptors and mediated by the Ca2+-dependent cytosolic protease calpain (10Hell J.W. Westenbroek R.E. Breeze L.J. Wang K.K.W. Chavkin C. Catterall W.A. Proc. Natl. Acad. Sci. U. S. A. 1996; 93: 3362-3367Crossref PubMed Scopus (175) Google Scholar). C-terminal truncation increases the activity of this channel about 4-fold (11Wei X. Neely A. Lacerda A.E. Olcese R. Stefani E. Perez-Reyes E. Birnbaumer L. J. Biol. Chem. 1994; 269: 1635-1640Abstract Full Text PDF PubMed Google Scholar). In contrast to α1D, α1C immunoreactivity has a punctate pattern consistent with a synaptic location (7Hell J.W. Westenbroek R.E. Warner C. Ahlijanian M.K. Prystay W. Gilbert M.M. Snutch T.P. Catterall W.A. J. Cell Biol. 1993; 123: 949-962Crossref PubMed Scopus (648) Google Scholar). This pattern of α1Cimmunoreactivity is detected at neuronal somata and proximal dendrites in most areas of the brain and in the hippocampus throughout the dendritic regions. Localization of α1C was further established by immunoelectron microscopy which disclosed that class C L-type channels are clustered at postsynaptic sites of excitatory synapses in the hippocampus (10Hell J.W. Westenbroek R.E. Breeze L.J. Wang K.K.W. Chavkin C. Catterall W.A. Proc. Natl. Acad. Sci. U. S. A. 1996; 93: 3362-3367Crossref PubMed Scopus (175) Google Scholar). 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The PKA holoenzyme is to a variety of and by proteins protein kinase A anchor proteins or 1994; Google Scholar, Catterall W.A. 1998; PubMed Scopus Google Scholar). The subunits bind with a of an in The site is the 1994; Google Scholar, Catterall W.A. 1998; PubMed Scopus Google Scholar). to the site of glutamate receptors in neurons C. Nature. 1994; PubMed Scopus Google Scholar) and of L-type channels in Catterall W.A. Proc. Natl. Acad. Sci. U. S. A. 1994; PubMed Scopus Google Scholar). is that PKA is at or for their efficient phosphorylation and and the class C Ca2+ channel in the postsynaptic membrane of mechanism that could rapid and of by to the channel the direct a complex and the target channel. We that the neuronal class C L-type Ca2+ channel complex PKA as well as MAP2B, a neuronal AKAP J. Cell Biol. PubMed Scopus Google Scholar, J. Full Text PDF PubMed Scopus Google Scholar). neuronal including or were not evident in the channel The and protein were from was from protein from from and from PKA and by established L.K. U. Proc. Natl. Acad. Sci. U. S. A. 77: PubMed Scopus Google Scholar, Biochem. 1987; PubMed Scopus Google Scholar, J. Biol. Chem. 1993; 268: Full Text PDF PubMed Google Scholar) were from and J. of of The PKA inhibitory peptide PKI(5–24) and were from L. of other were from and were of the protease were A and calpain and The and were to and in the cytosolic two and of α1C and and as (7Hell J.W. Westenbroek R.E. Warner C. Ahlijanian M.K. Prystay W. Gilbert M.M. Snutch T.P. Catterall W.A. J. Cell Biol. 1993; 123: 949-962Crossref PubMed Scopus (648) Google Scholar, J.W. Yokoyama C.T. Wong S.T. Warner C. Snutch T.P. Catterall W.A. J. Biol. Chem. 1993; 268: 19451-19457Abstract Full Text PDF PubMed Google Scholar, J. Ahlijanian M.K. Catterall W.A. Snutch T.P. Proc. Natl. Acad. Sci. U. S. A. PubMed Scopus Google Scholar, J.W. Yokoyama C.T. Warner C. Catterall W.A. J. Biol. Chem. 1994; 269: Full Text PDF PubMed Google Scholar). for the PKA phosphorylation site at serine in a peptide with the serine was by by to and for the of as J.W. Catterall W.A. Biochem. 1996; PubMed Scopus Google Scholar). of the of was in of in the of protease and the and of were and the was by were by the peptide to for as (7Hell J.W. Westenbroek R.E. Warner C. Ahlijanian M.K. Prystay W. Gilbert M.M. Snutch T.P. Catterall W.A. J. Cell Biol. 1993; 123: 949-962Crossref PubMed Scopus (648) Google Scholar). The is the subunit in N. J. Biol. Chem. Full Text PDF PubMed Google Scholar) and was by R. J. of the C subunit of PKA and were and as R.E. S. X. J. Biol. Chem. 1990; Full Text PDF PubMed Google Scholar, Biol. PubMed Scopus Google Scholar, C. Y. J. Biol. Chem. 1993; 268: Full Text PDF PubMed Google Scholar). The J. Cell Biol. PubMed Scopus Google Scholar) was a from X. of of and were from were from were performed at from were directly in and protease were and in a and in of to of the of α1C for extracts and calpain and were was by for at membrane were for rat were in of if and protease were at for at to including were by for at and the and as a of MAP2B for in vitro with from rat were in of and by as the of MAP2B by from rat were in of and protease for at was by addition of of and by which bind to were by with of of for and with a extracts were with either of of of of or of of protein and with were and the were a for at The were by and with in and with were either with of and for at and to (7Hell J.W. Westenbroek R.E. Warner C. Ahlijanian M.K. Prystay W. Gilbert M.M. Snutch T.P. Catterall W.A. J. Cell Biol. 1993; 123: 949-962Crossref PubMed Scopus (648) Google Scholar) or as for kinase or MAP2B association endogenous MAP2B directly to were performed with (8Hell J.W. Yokoyama C.T. Wong S.T. Warner C. Snutch T.P. Catterall W.A. J. Biol. Chem. 1993; 268: 19451-19457Abstract Full Text PDF PubMed Google Scholar, J.W. Yokoyama C.T. Breeze L.J. Chavkin C. Catterall W.A. J. 1995; PubMed Scopus Google Scholar) of heart were with of dissociation protease for at in a with of dilution and protease in and were with or and protein as were for a with of the cytosolic brain with in and with and by immunoblotting. In MAP2B binding MAP2B was to by immunoprecipitation from brain membrane extracts with and protein by the for the immunoprecipitation MAP2B was with dissociation addition of a of dilution with protein from by immunoprecipitation The of MAP2B isolated by immunoprecipitation was by and and immunoblotting. from and proteins were to pore were for with in and for with in in C subunit in in in in or in were with for with or and in for with in with at and with were in of phosphorylation A This was with of and of for phosphorylation in the of were with of PKA or and immunoblotting with or in a for at with and in Phosphorylation of α1C by endogenous kinase was as kinase in the or of cAMP. The were with and immunoblotting with or with were with of in for at in a and with in and in were by endogenous kinase with in the or of and for at immunoblotting with were in phosphorylation in the or of and of were and in a for at The were by addition of The were The was for with and of by the PKA of the the with addition of were from the were with and proteins were by as N. J. Biol. Chem. 264: Full Text PDF PubMed Google Scholar, J. Biol. Chem. Full Text PDF PubMed Google Scholar). which is only in the of has identified as the main if not only phosphorylation site for PKA in this subunit J.W. Catterall W.A. Biochem. 1996; PubMed Scopus Google Scholar). a that at serine with a peptide of The detected a brain in the of was for immunoblotting. The with an of in a gel from and the of a gel from a classic of the of α1C indicate that the of α1C with α1C has to be by PKA for class C channels were with in the of and with which is a in the part of these α1C be by in the and is not by if the α1C was with PKA detected α1C This phosphorylation was mediated by PKA was by the PKI(5–24) peptide L.M. R. J. Biol. Chem. 1996; Full Text Full Text PDF PubMed Scopus Google a peptide derived from the endogenous PKA and α1C with only α1C is at PKA The findings also indicate that α1C is serine in serine a for phosphorylation by of class C channel with and also in phosphorylation of serine the phosphorylation was by the peptide phosphorylation of serine was by endogenous PKA that with the class C channel. ensure that was and of α1C as (8Hell J.W. Yokoyama C.T. Wong S.T. Warner C. Snutch T.P. Catterall W.A. J. Biol. Chem. 1993; 268: 19451-19457Abstract Full Text PDF PubMed Google the was with and and by and The kDa) of which is not a PKA was as as the In in several experiments a was the of were detected in immunoprecipitates isolated with that of class C channels was were in the of to endogenous protein with and immunoblotting with that serine in was by an endogenous kinase the in Phosphorylation was by the peptide, that PKA is the endogenous kinase In the PKA activity of the C subunit is inhibited by the R subunit is in the phosphorylation that the PKA holoenzyme is with class C channels. Phosphorylation in the of is to the that a of and the of and dissociation of C subunit J. Biol. Chem. Full Text PDF PubMed Google Scholar). important with to PKA at substrate sites is the catalytic subunit from the AKAP complex or if the C subunit is is possible that either not cause dissociation of the C subunit from the R subunit catalytic activity S. 1995; PubMed Scopus Google Scholar) or that C subunit the channel complex a were by the class C channel with cAMP. was Ca2+ channel activity evident and the was stimulated by This activity was by the inhibitory peptide activity was channel were with C subunit was by In not all a dissociation of C at findings suggest that the PKA holoenzyme to the channel is in the of J. Biol. Chem. Full Text PDF PubMed Google Scholar). suggest that the C subunit from the the of the C subunit and the complex in the of which may the C subunit in the complex in may be disrupted of the of PKA with class C channels was by immunoblotting and Class C channel and receptors were from extracts of rat brain with and was also performed with C subunit was only detected in the class C channel The of the of PKA activity with class C channels was further confirmed by a peptide phosphorylation assay were phosphorylation with and kemptide, a substrate peptide for PKA L.M. R. J. Biol. Chem. 1996; Full Text Full Text PDF PubMed Scopus Google Scholar). Phosphorylation of was performed in the and of the inhibitory phosphorylation was and may activity of is the the and the which is mediated by PKA activity was in class C channel or immunoprecipitates these show that the of PKA in class C channel is not to PKA and either or protein PKA not bind to other integral membrane proteins as receptors in an activity is in class C channel complexes. were with and with or were with and for in the or of of was by and PKA activity is as the and with are as which AKAP is in the class C channel complex and may mediate of protein overlay RIIβ subunits were performed N. J. Biol. Chem. 264: Full Text PDF PubMed Google Scholar, U. Proc. Natl. Acad. Sci. U. S. A. PubMed Scopus Google Scholar). Two proteins were evident in extracts of brain The M r of the polypeptides that to two brain MAP2B J. Cell Biol. PubMed Scopus Google Scholar, J. Full Text PDF PubMed Scopus Google Scholar) and Biol. PubMed Scopus Google Scholar, N. J. Biol. Chem. 264: Full Text PDF PubMed Google Scholar). The AKAP was in class C channel isolated by immunoprecipitation This was for the class C channel was for or and The of the protein in membrane was established as MAP2B by immunoblotting MAP2B was with the class C channel isolated by immunoprecipitation The MAP2B and the Ca2+ channel was MAP2B was from with or and and J. Biol. Chem. 1996; Full Text Full Text PDF PubMed Scopus Google Scholar) were evident in membrane extracts these anchor proteins were not with class C channels or receptors and Class C L-type channels are and clustered in dendritic the postsynaptic sites of excitatory synapses (10Hell J.W. Westenbroek R.E. Breeze L.J. Wang K.K.W. Chavkin C. Catterall W.A. Proc. Natl. Acad. Sci. U. S. A. 1996; 93: 3362-3367Crossref PubMed Scopus (175) Google Scholar). MAP2B is a microtubule-associated protein in the brain are not in postsynaptic Annu. Rev. 1994; PubMed Scopus Google Scholar). MAP2B has to be in dendritic by A. L. J. PubMed Google Scholar). Accordingly, MAP2B may not only with may also bind to other proteins of suggest that MAP2B and class C channels are in the subcellular could with the that MAP2B binding to class C channels formed of the protein with was to the This and of tubulin which is in the extracts of extracts in the of nocodazole, MAP2B was with class C channel The of MAP2B with the class C channel complex to membrane upon addition of A and MAP2B immunoreactivity was in of class B N-type Ca2+ channels which a of with class C channels are at sites R.E. J.W. Warner C. Snutch T.P. Catterall W.A. Full Text PDF PubMed Scopus Google Scholar) or in other and tubulin was in the was not in class C channel indicate that the class C channels and MAP2B not and is not mediated by the that MAP2B binding to class C channels or brain was at dilution of of in the of and were by and channels were with and as MAP2B with the class C channel proteins these The of MAP2B to class C channels was not to membrane by the dilution B and This that the of MAP2B in the class C channel is not to association of the brain in vitro an that may in The of the was by immunoblotting for the glutamate and Ca2+ channel protein in the A. and J. W. Class C channel consist of several subunits including α2δ, and β (6Catterall W.A. Annu. Rev. Biochem. 1995; 64: 493-531Crossref PubMed Scopus (781) Google Scholar). MAP2B directly to of the that class C channels not MAP2B are in the Class C channels were from were with at and α1C was This of α1C in the of other channel subunits or proteins (8Hell J.W. Yokoyama C.T. Wong S.T. Warner C. Snutch T.P. Catterall W.A. J. Biol. Chem. 1993; 268: 19451-19457Abstract Full Text PDF PubMed Google Scholar, J.W. Westenbroek R.E. Breeze L.J. Wang K.K.W. Chavkin C. Catterall W.A. Proc. Natl. Acad. Sci. U. S. A. 1996; 93: 3362-3367Crossref PubMed Scopus (175) Google Scholar, J.W. Yokoyama C.T. Breeze L.J. Chavkin C. Catterall W.A. J. 1995; PubMed Scopus Google Scholar). or were in the or of brain which is a of The cytosolic by to microtubules. MAP2B to forms of α1C not to immunoprecipitates with MAP2B was in from heart brain was Accordingly, α1C is for MAP2B the C-terminal in the not of α1C is for MAP2B heart extracts were in the of and calpain these the of MAP2B to the that the C terminus of the is not for MAP2B is possible that MAP2B binding to α1C protein in the cytosolic that as of this MAP2B was by immunoprecipitation with the were by and only two were with in the of and The is most the MAP2B this with MAP2B immunoreactivity as by immunoblotting of part of the gel the gel and to proteins the The other at is the of the in the immunoprecipitation was contrast to the also in the further the of the at and to the of an in the MAP2B that with the of the the MAP2B and were also by in the of these the was the and two and two to the complex of two and two and to the This the of MAP2B by this immunoprecipitation MAP2B was from the with which was by an of The was to which in from heart extracts by these the MAP2B to the α1C not to a α1C did not contain endogenous MAP2B and tubulin was not in of these that nor tubulin is for MAP2B these show that MAP2B can directly with α1C is an substrate for phosphorylation by PKA the association of MAP2B with the class C channel. Class C channel were immunoisolated and phosphorylation further and immunoblotting with and MAP2B association with the channel was not upon phosphorylation by either endogenous or PKA as in the of the phosphorylation to phosphorylation of α1C the in with at of of phosphorylation sites are (8Hell J.W. Yokoyama C.T. Wong S.T. Warner C. Snutch T.P. Catterall W.A. J. Biol. Chem. 1993; 268: 19451-19457Abstract Full Text PDF PubMed Google Scholar). findings suggest that phosphorylation of α1C by PKA not the MAP2B and of PKA to be for efficient phosphorylation and of and voltage-gated channels, including receptors and L-type channels A. H. S.A. N. M.M. 1997; Full Text Full Text PDF PubMed Scopus Google Scholar, C. Nature. 1994; PubMed Scopus Google Catterall W.A. Proc. Natl. Acad. Sci. U. S. A. 1994; PubMed Scopus Google Scholar). is are PKA substrates. Our suggest that the class C L-type Ca2+ channel complex a site for an We that the AKAP MAP2B with the neuronal class C channels. MAP2B was the only AKAP in class C channel complexes. Neither nor were detected in class C channel by overlay or immunoblotting. a anchor protein is in recruiting PKA to the L-type channel Catterall W.A. J. Biol. Chem. 1997; Full Text Full Text PDF PubMed Scopus Google Scholar, Westenbroek R.E. Catterall W.A. 1998; Full Text Full Text PDF PubMed Scopus Google Scholar, Tavalin L.K. R.A. N.V. J. 1998; PubMed Scopus Google Scholar). is also in heart and The overlay binding did not in class C L-type channel isolated by immunoprecipitation from heart or brain A. C. S. and J. W. may not mediate PKA association with neuronal or class C channels. A revealed that is with channels in brain Catterall W.A. J. Biol. Chem. 1998; Full Text Full Text PDF PubMed Scopus (70) Google Scholar). may PKA to subcellular channels class C channels. show that MAP2B association with the class C channel is with to the channel and the AKAP. MAP2B did not bind receptors or class B N-type channels and other were with class C channels. Class C L-type channels are clustered in dendritic (10Hell J.W. Westenbroek R.E. Breeze L.J. Wang K.K.W. Chavkin C. Catterall W.A. Proc. Natl. Acad. Sci. U. S. A. 1996; 93: 3362-3367Crossref PubMed Scopus (175) Google Scholar). In a of MAP2B is with which are in dendritic Annu. Rev. 1994; PubMed Scopus Google Scholar). MAP2B immunoreactivity is evident in dendritic and postsynaptic A. L. J. PubMed Google Scholar). Accordingly, MAP2B may bind to protein other at postsynaptic sites. The α1C subunit of neuronal L-type channel to be a for MAP2B at postsynaptic sites. Like L-type channels A. H. S.A. N. M.M. 1997; Full Text Full Text PDF PubMed Scopus Google Scholar, Catterall W.A. Proc. Natl. Acad. Sci. U. S. A. 1994; PubMed Scopus Google receptors PKA for efficient phosphorylation and C. Nature. 1994; PubMed Scopus Google Scholar). two immunoblotting with subunit and the phosphorylation assay to PKA in a complex with be that association of PKA with receptors is mediated by that are not to and immunoprecipitation were and did not or as is for protein J.W. J. Biol. Chem. 1997; Full Text Full Text PDF PubMed Scopus Google Scholar, M.C. J.W. J. Biol. Chem. 1998; Full Text Full Text PDF PubMed Scopus Google Scholar). the were to show by immunoblotting as well as the phosphorylation assay that PKA is with class C channel that are to the of and channels. possible that PKA in the of receptors postsynaptic protein that as for the immunoelectron microscopy of class C channels a postsynaptic pattern to that of receptors (10Hell J.W. Westenbroek R.E. Breeze L.J. Wang K.K.W. Chavkin C. Catterall W.A. Proc. Natl. Acad. Sci. U. S. A. 1996; 93: 3362-3367Crossref PubMed Scopus (175) Google Scholar, J. PubMed Scopus Google is to that of MAP2B to postsynaptic sites by class C channels may phosphorylation of Our the an MAP2B, and a the class C L-type Ca2+ that is an integral and of the postsynaptic of excitatory The class C channel a in recruiting PKA to the postsynaptic channel complex by a site for Accordingly, class C channels may be for postsynaptic of PKA which is an important in of synaptic including synaptic and We are to R. J. of for the L. of for the and X. of for the and J. of for
Davare et al. (Fri,) reported a other. PKA is an integral part of neuronal class C L-type Ca2+ channels, and the A-kinase anchor protein MAP2B directly binds to the alpha1 subunit to mediate this interaction.