Enlightening the Postsynaptic Density
Authors: Edward B Ziff
Journal: Neuron (1997)

The postsynaptic density (PSD) is a specialization of the cytoskeleton at the synaptic junction. It lies adjacent to the cytoplasmic face of the postsynaptic membrane, in close apposition to the active zone of the synapse and the docked synaptic vesicles in the presynaptic terminal. Emerging evidence indicates that the PSD provides multiple functions and is an essential component of an extraordinary synaptic signaling assemblage. The PSD forms a disc that consists of cytoskeletal and regulatory proteins, some of which contact the cytoplasmic domains of ion channels in the postsynaptic membrane. This location places the PSD directly in the path of the intracellular ionic fluxes and second messenger cascades generated by neurotransmitters. It is now apparent that the PSD provides a structural matrix, which clusters ion channels in the postsynaptic membrane (reviewed by73Kennedy M.B The postsynaptic density.Curr. Opin. 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These properties suggest that the PSD serves as a general organizer of the postsynaptic signal transduction machinery, which links regulatory molecules to their targets, coordinates developmental and activity-dependent changes in postsynaptic structures, and establishes the functional topography of the postsynaptic membrane. Important mechanisms for synaptic regulation, including long-term potentiation (LTP) and long-term depression (LTD), are likely to have a basis in the PSD. For example, a major component of the PSD, the α subunit of the Ca2+/calmodulin-dependent protein kinase II (αCaMKII; 76Kennedy M.B Bennett M.K Erondu N.E Biochemical and immunochemical evidence that the "major postsynaptic density protein" is a subunit of a calmodulin-dependent protein kinase.Proc. Natl. Acad. Sci. USA. 1983; 80: 7357-7361Crossref PubMed Google Scholar, 49Goldenring J.R McGuire J.J DeLorenzo R.J Identification of the major postsynaptic density protein as homologous with the major calmodulin-binding subunit of a calmodulin-dependent protein kinase.J. Neurochem. 1984; 42: 1077-1084Crossref PubMed Google Scholar, 72Kelly P.T McGuinness T.L Greengard P Evidence that the major postsynaptic density protein is a component of a Ca2+/calmodulin-dependent protein kinase.Proc. Natl. Acad. Sci. USA. 1984; 81: 945-949Crossref PubMed Google Scholar), has a central role in a current model for long-term memory (113Miller S.G Kennedy M.B Regulation of brain type II Ca2+/calmodulin-dependent protein kinase by autophosphorylation a Ca2+-triggered molecular switch.Cell. 1986; 44: 861-870Abstract Full Text PDF PubMed Scopus (0) Google Scholar, 103Lisman J.E Goldring M.A Feasibility of long-term storage of graded information by the Ca2+/calmodulin-dependent protein kinase molecules of the postsynaptic density.Proc. Natl. Acad. Sci. USA. 1988; 85: 5320-5324Crossref PubMed Google Scholar). The NMDA receptor, which is required for several forms of synaptic plasticity (reviewed by158Wilson M.A Tonegawa S Synaptic plasticity, place cells and spatial memory study with second generation knockouts.Trends Neurosci. 1997; 20: 102-106Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar), is clustered at the synapse by components of the PSD (reviewed by138Sheng M Kim E Ion channel associated proteins.Curr. Opin. Neurobiol. 1996; 6: 602-608Crossref PubMed Scopus (0) Google Scholar). Thus, the PSD contributes to critical features of synaptic integration and regulation. Junctional structures of neurons were first detected by the electron microscope in the 1950s as electron-dense specializations of pre- and postsynaptic membranes at the neuromuscular junction and at points of contact between cortical neurons at chemically transmitting synapses (28De Robertis E Bennett H.S Submicroscopic vesicular component in the synapse.Fed. Proc. 1954; 13: 35Google Scholar, 122Palade G.E Palay S.L Electron microscope observations of interneuronal and neuromuscular synapses.Anat. Rec. 1954; 118: 335-336Google Scholar). In 1958, Palay observed that facing the nerve terminal, "the opposite postsynaptic membrane is … thickened and denser than it is elsewhere." This highly differentiated structure, shown for hippocampal CA1 and Purkinje cell synapses in Figure 1, was called variously the postsynaptic thickening, the postsynaptic web, or the postsynaptic density. Typical PSDs are observed at type 1 glutamatergic excitatory synapses and are the focus of this review. A somewhat different PSD is seen at type 2 GABAergic and glycinergic inhibitory synapses (52Gray E.C Axo-somatic and axo-dendritic synapses of cerebral cortex. An electron microscopic study.J. Anat. 1959; 93: 420-433PubMed Google Scholar, 25Colonnier M Synaptic patterns on different cell types in the different laminae of the cat visual cortex. An electron microscope study.Brain Res. 1968; 9: 268-287Crossref PubMed Google Scholar, 96Landis D.M Reese T.S Differences in membrane structure between excitatory and inhibitory synapses in the cerebellar cortex.J. Comp. Neurol. 1974; 155: 93-125Crossref PubMed Google Scholar, 98Landis D.M Reese T.S Raviola E Differences in membrane structure between excitatory and inhibitory components of the reciprocal synapse in the olfactory bulb.J. Comp. Neurol. 1974; 155: 67-91Crossref PubMed Google Scholar, 127Peters A Palay S.L Webster H.D The Fine Structure of the Nervous System. 3. Oxford University Press, New York1991Google Scholar). Related structures are also found at the neuromuscular junction (134Sanes J.R Genetic analysis of postsynaptic differentiation at the vertebrate neuromuscular junction.Curr. Opin. Neurobiol. 1997; 7: 93-100Crossref PubMed Scopus (0) Google Scholar). Major morphological variants of type 1 synapses include axodendritic synaptic junctions formed on dendritic shafts, nonperforated axospinous synapses with a continuous PSD, and perforated synapses with a segmented PSD (127Peters A Palay S.L Webster H.D The Fine Structure of the Nervous System. 3. Oxford University Press, New York1991Google Scholar). The PSD has a diffuse cytoplasmic boundary, which suggests a fibrillar structure (Figure 2A), and filamentous components are visible in freeze fracture preparations (Figure 2B). The PSD is gently curved and follows the contour of the spine head and is almost invariably found in direct apposition to the active zone, facing membrane-docked vesicles of the presynaptic nerve terminal. The mechanism that establishes this placement is not known. However, the apposition is often maintained in perforated synapses, in which two neighboring synaptic active zones are separated by a region lacking pre- and postsynaptic specializations (Figure 1A). Perforated PSDs are found in dendritic spines of dentate gyrus neurons (45Geinisman Y Morrell F de Toledo-Morrell L Axospinous synapses with segmented postsynaptic densities a morphologically distinct synaptic subtype contributing to the number of profiles of "perforated" synapses visualized in random sections.Brain Res. 1987; 423 (a): 179-188Crossref PubMed Google Scholar, 46Geinisman Y Morrell F de Toledo-Morrell L Synapses on dendritic shafts exhibit a perforated postsynaptic density.Brain Res. 1987; 422 (b): 352-356Crossref PubMed Google Scholar) and can result in separated transmission zones (44Geinisman Y Perforated axospinous synapses with multiple, completely partitioned transmission zones probable structural intermediates in synaptic plasticity.Hippocampus. 1993; 3: 417-433Crossref PubMed Scopus (0) Google Scholar). The molecular mechanisms that align the pre- and postsynaptic submembraneous structures are not known, but at glutamatergic synapses, it may be provided by densin 180 or related proteins. Densin 180 is an O-sialo glycoprotein related to adhesion molecules that is concentrated in membranes at synapses of the forebrain (5Apperson M.L Moon I.S Kennedy M.B Characterization of densin-180, a new brain-specific synaptic protein of the O-sialoglycoprotein family.J. Neurosci. 1996; 16: 6839-6852Crossref PubMed Google Scholar). Interactions of the cadherins and the neuroligans and neurexins have also recently been implicated in this alignment (37Fannon A.M Colman D.R A model for central synaptic junctional complex formation based on the differential adhesive specificities of the cadherins.Neuron. 1996; 17: 423-434Abstract Full Text Full Text PDF PubMed Scopus (344) Google Scholar, 66Irie M Hata Y Takeuchi M Ichtchenko K Toyoda A Hirao K Takai Y Rosahl T.W Sudhof T.C Binding of neuroligins to PSD-95.Science. 1997; 277: 1511-1515Crossref PubMed Scopus (493) Google Scholar; see below). The nonperforated or simple PSD and the peforated PSD may have a precursor–product relationship, in which the perforated PSD is an intermediate in synapse turnover, duplication, or synaptic activation (17Carlin R.K Siekevitz P Plasticity in the central nervous system do synapses divide?.Proc. Natl. Acad. Sci. USA. 1983; 80: 3517-3521Crossref PubMed Google Scholar, 33Edwards F.A LTP—a structural model to explain the inconsistencies.Trends Neurosci. 1995; 18: 250-255Abstract Full Text PDF PubMed Google Scholar). Since LTP may increase the number of synapses with segmented PSDs (47Geinisman Y Morrell F de Toledo-Morrell L Increase in the number of axospinous synapses with segmented postsynaptic densities following hippocampal kindling.Brain Res. 1992; 569: 341-347Crossref PubMed Scopus (0) Google Scholar, 15Buchs P.A Muller D Induction of long-term potentiation is associated with major ultrastructural changes of activated synapses.Proc. Natl. Acad. Sci. USA. 1996; 93: 8040-8045Crossref PubMed Scopus (0) Google Scholar), synaptic activity may control PSD morphology. Synaptic junctional complexes can be isolated from the brain by nonionic detergent extraction of synaptic membrane preparations (40Fiszer S De Robertis L Action of Triton X-100 on ultrastructure and membrane-bound enzymes of isolated nerve endings from rat brain.Brain Res. 1967; 5: 31-44Crossref PubMed Google Scholar, 24Cohen R.S Blomberg F Berzins K Siekevitz P The structure of postsynaptic densities isolated from dog cerebral cortex. I. Overall morphology and protein composition.J. Cell Biol. 1977; 74: 181-203Crossref PubMed Google Scholar, 18Carlin R.K Grab D.J Cohen R.S Siekevitz P Isolation and characterization of postsynaptic densities from various brain regions enrichment of different types of postsynaptic densities.J. Cell Biol. 1980; 86: 831-845Crossref PubMed Google Scholar). Electron microscopy indicates an organized ultrastructure. Isolated PSDs appear as semicircular bands (Figure 3), lacking a recognizable boundary and measuring about 400 nm long and 40 nm wide. Isolated PSDs stain densely and are composed of both filamentous and particulate components. When viewed from the side, the isolated PSD often resembles a concave disk. Concanavalin A–binding sites indicative of glycoproteins marking the extracellular side are restricted to one surface of the PSD when the PSD is prepared to retain the postsynaptic plasma membrane (55Gurd J.W Gordon W.P Evans W.H Identification and localization of concanavalin A binding sites on isolated postsynaptic densities.Brain Res. 1983; 276: 141-146Crossref PubMed Scopus (0) Google Scholar). The major ConA–binding protein was identified as the NMDA receptor subunit NR2B (114Moon I.S Apperson M.L Kennedy M.B The major tyrosine-phosphorylated protein in the postsynaptic density fraction is N-methyl-D-aspartate receptor subunit 2B.Proc. Natl. Acad. Sci. USA. 1994; 91: 3954-3958Crossref PubMed Google Scholar). When freed of its membrane attachments, the PSD in some cases displays a central hole (23Cohen R.S Siekevitz P Form of the postsynaptic density. A serial section study.J. Cell Biol. 1978; 78: 36-46Crossref PubMed Google Scholar). The PSD can assume a loose web-like structure with subsynaptic particulate bodies on the cytoplasmic side (24Cohen R.S Blomberg F Berzins K Siekevitz P The structure of postsynaptic densities isolated from dog cerebral cortex. I. Overall morphology and protein composition.J. Cell Biol. 1977; 74: 181-203Crossref PubMed Google Scholar) and may be dissociated into finely striated strips by N-lauroyl sarcosinate treatment (149Suzuki T Tanaka R Postsynaptic density visualized by whole mount electron microscopy.Neurosci. Res. 1986; 3: 226-236Crossref PubMed Google Scholar). The filamentous components appear to hold together the particulate components. In one deep-etch, freeze fracture study, 4 nm filaments tentatively identified as F-actin were intermeshed with 8–9 nm filaments, which were concentrated below the PSD (53Gulley R.L Reese T.S Cytoskeletal organization at the postsynaptic complex.J. Cell Biol. 1981; 91: 298-302Crossref PubMed Google Scholar). This suggested that the 4 nm filaments may limit the mobility of receptors by anchoring them to the microfilament lattice and that this connection may also maintain the curvature of the postsynaptic membrane. Filaments of 5–7 nm, which constitute the submembrane cytoskeleton of the spine and which insert in the membrane in the midst of the PSD, may be brain spectrin (97Landis D.M Reese T.S Cytoplasmic organization in cerebellar dendritic spines.J. Cell Biol. 1983; 97: 1169-1178Crossref PubMed Google Scholar). similar observations have been made at hippocampal synapses using rapid freezing methods (130Pozzo-Miller L Landis D.M Cytoplasmic structure in organotypic cultures of rat hippocampus prepared by rapid freezing and freeze-substitution fixation.Synapse. 1993; 13: 195-205Crossref PubMed Google Scholar). In Purkinje cell dendritic spines, actin-like and spectrin-like microfilaments are juxtaposed to the PSD but do not appear to be continuous with the filaments of the PSD itself (99Landis D.M Weinstein L.A Reese T.S Substructure in the postsynaptic density of Purkinje cell dendritic spines revealed by rapid freezing and etching.Synapse. 1987; 1: 552-558Crossref PubMed Google Scholar). Globular proteins appear at irregular intervals on the filamentous net of the PSD and are positioned at sites expected to have the greatest Ca2+ ion fluxes during NMDA receptor activation. Electron microscopy also reveals interactions between the PSD and organelles of the dendritic spine. Smooth endoplasmic reticulum cisterns are found in the spine (reviewed by38Fifkova E Morales M Actin matrix of dendritic spines, synaptic plasticity, and long-term potentiation.Int. Rev. Cytol. 1992; 139: 267-307Crossref PubMed Google Scholar) and in some cases reach the margins of the PSD (142Spacek J Harris K.M Three-dimensional organization of smooth endoplasmic reticulum in hippocampal CA1 dendrites and dendritic spines of the immature and mature rat.J. Neurosci. 1997; 17: 190-203Crossref PubMed Google Scholar). This so-called spine apparatus consisting of irregular, membranous, electron-dense sac-like structures running through the neck of the spine (142Spacek J Harris K.M Three-dimensional organization of smooth endoplasmic reticulum in hippocampal CA1 dendrites and dendritic spines of the immature and mature rat.J. Neurosci. 1997; 17: 190-203Crossref PubMed Google Scholar) may be an extension of the dendritic smooth endoplasmic reticulum. The PSD and spine apparatus appear to be interconnected by actin filaments. However, the actin filaments may be distinct from a PSD core, which contains regulatory components such as αCaMKII (2Adam G Matus A Role of actin in the organisation of brain postsynaptic densities.Brain Res. Mol. Brain Res. 1996; 43: 246-250Crossref PubMed Scopus (0) Google Scholar). The cytoarchitecture of the spine is thought to be in dynamic flux. Actin concentrations are high in the spine, and actin polymerization is under the negative control of Ca2+ fluxes (reviewed by38Fifkova E Morales M Actin matrix of dendritic spines, synaptic plasticity, and long-term potentiation.Int. Rev. Cytol. 1992; 139: 267-307Crossref PubMed Google Scholar). Changes in Ca2+ concentration within individual spines (56Guthrie P.B Segal M Kater S.B Independent regulation of calcium revealed by imaging dendritic spines.Nature. 1991; 354: 76-80Crossref PubMed Google Scholar, 115Muller W Connor J.A Dendritic spines as individual neuronal compartments for synaptic Ca2+ responses.Nature. 1991; 354: 73-76Crossref PubMed Google Scholar, 131Pozzo-Miller L Petrozzino J.J Mahanty N.K Connor J.A Optical imaging of cytosolic calcium, electrophysiology and ultrastructure in pyramidal neurons of organotypic slice cultures from rat hippocampus.Neuroimage. 1993; 1: 109-120Crossref PubMed Google Scholar, 68Jaffe D.B Fisher S.A Brown T.H Confocal laser scanning microscopy reveals voltage-gated calcium signals within hippocampal dendritic spines.J. Neurobiol. 1994; 25: 220-233Crossref PubMed Google Scholar, 27Denk W Sugimori M Llinas R Two types of calcium response limited to single spines in cerebellar Purkinje cells.Proc. Natl. Acad. Sci. 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The first efforts to identify the protein components of the PSD employed detergent extraction of brain tissue and differential centrifugation to purify biochemical quantities of a PSD fraction. Further fractionation led to the isolation of individual PSD proteins. Systematic studies identified over 30 PSD constituents, including cytoskeletal and neurofilament proteins, enzymes of glycolysis, heatshock and vesicle transport proteins, plus a class of high Mr proteins (156Walsh M.J Kuruc N The postsynaptic density constituent and associated proteins characterized by electrophoresis, immunoblotting, and peptide sequencing.J. Neurochem. 1992; 59: 667-678Crossref PubMed Scopus (0) Google Scholar, 100Langnaese K Seidenbecher C Wex H Seidel B Hartung K Appeltauer U Garner A Voss B Mueller B Garner C.C Gundelfinger E.D Protein components of a rat brain synaptic junctional protein preparation.Brain Res. Mol. Brain Res. 1996; 42: 118-122Crossref PubMed Scopus (0) Google Scholar). When the PSD is purified by mild nonionic detergent extraction of brain tissue, the PSD is released in a complex with glycoproteins of the postsynaptic membrane (55Gurd J.W Gordon W.P Evans W.H Identification and localization of concanavalin A binding sites on isolated postsynaptic densities.Brain Res. 1983; 276: 141-146Crossref PubMed Scopus (0) Google Scholar), some of which were later identified as ion channels. The ionotropic NMDA and AMPA-type of glutamate receptors and the metabotropic glutamate receptors are concentrated in the postsynaptic membrane of excitatory synapses in association with the PSD (120Nusser Z Mulvihill E Streit P Somogyi P Subsynaptic segregation of metabotropic and ionotropic glutamate receptors as revealed by immunogold localization.Neuroscience. 1994; 61: 421-427Crossref PubMed Scopus (0) Google Scholar). Other cell junction proteins are also found, including N-cadherin (8Beesley P.W Mummery R Tibaldi J N-cadherin is a major glycoprotein component of isolated rat forebrain postsynaptic densities.J. Neurochem. 1995; 64: 2288-2294Crossref PubMed Google Scholar, 165Yamagata M Herman J.P Sanes J.R Lamina-specific expression of adhesion molecules in developing chick optic tectum.J. Neurosci. 1995; 15: 4556-4571Crossref PubMed Google Scholar, 155Uchida N Honjo Y Johnson K.R Wheelock M.J Takeichi M The catenin/cadherin adhesion system is localized in synaptic junctions bordering transmitter release zones.J. Cell Biol. 1996; 135: 767-779Crossref PubMed Scopus (394) Google Scholar). Given the fibrillar character of the PSD, it was not suprising that components of the cytoskeleton are also abundant, including actin (38Fifkova E Morales M Actin matrix of dendritic spines, synaptic plasticity, and long-term potentiation.Int. Rev. 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Calcium/calmodulin-regulated capping of the barbed ends of actin filaments.J. Biol. Chem. 1996; 271: 7986-7991Crossref PubMed Scopus (161) Google Scholar, 110Matsuoka Y Hughes C.A Bennett V Adducin regulation. Definition of the calmodulin-binding domain and sites of phosphorylation by protein kinases A and C.J. Biol. Chem. 1996; 271: 25157-25166Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar). The precise molecular organization of these cytoskeletal components within the PSD is not yet known. Numerous regulatory molecules have also been localized to the PSD, including calmodulin (50Grab D.J Berzins K Cohen R.S Siekevitz P Presence of calmodulin in postsynaptic densities isolated from canine cerebral cortex.J. Biol. Chem. 1979; 254: 8690-8696PubMed Google Scholar) and αCaMKII (CaMKII) (76Kennedy M.B Bennett M.K Erondu N.E Biochemical and immunochemical evidence that the "major postsynaptic density protein" is a subunit of a calmodulin-dependent protein kinase.Proc. Natl. Acad. Sci. USA. 1983; 80: 7357-7361Crossref PubMed Google Scholar, 49Goldenring J.R McGuire J.J DeLorenzo R.J Identification of the major postsynaptic density protein as homologous with the major calmodulin-binding subunit of a calmodulin-dependent protein kinase.J. Neurochem. 1984; 42: 1077-1084Crossref PubMed Google Scholar, 72Kelly P.T McGuinness T.L Greengard P Evidence that the major postsynaptic density protein is a component of a Ca2+/calmodulin-dependent protein kinase.Proc. Natl. Acad. Sci. USA. 1984; 81: 945-949Crossref PubMed Google Scholar, 121Ouimet C.C McGuinness T.L Greengard P Immunocytochemical localization of calcium/calmodulin-dependent protein kinase II in rat brain.Proc. Natl. Acad. Sci. USA. 1984; 81: 5604-5608Crossref PubMed Google Scholar, 41Fukunaga K Goto S Miyamoto E Immunohistochemical localization of Ca2+/calmodulin-dependent protein kinase II in rat brain and various tissues.J. 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Following CaMKII autophosphorylation, which leads to calmodulin independence (113Miller S.G Kennedy M.B Regulation of brain type II Ca2+/calmodulin-dependent protein kinase by autophosphorylation a Ca2+-triggered molecular switch.Cell. 1986; 44: 861-870Abstract Full Text PDF PubMed Scopus (0) Google Scholar), CaMKII can translocate to the PSD (146Strack S Choi S Lovinger D.M Colbran R.J Translocation of autophosphorylated calcium/calmodulin-dependent protein kinase II to the postsynaptic density.J. Biol. Chem. 1997; 272 (b): 13467-13470Crossref PubMed Scopus (215) Google Scholar), where it may phosphorylate glutamate receptors (see below). Protein kinase C subtypes beta and gamma (159Wolf M Burgess S Misra U.K Sahyoun N Postsynaptic densities contain a subtype of protein kinase C.Biochem. Biophys. Res. 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Chem. 1992; 267: 16816-16823Abstract Full Text PDF PubMed Google Scholar), and the Fyn tyrosine kinase (148Suzuki T Okumura N.K NMDA receptor subunits epsilon 1 (NR2A) and epsilon 2 (NR2B) are substrates for Fyn in the postsynaptic density fraction isolated from the rat brain.Biochem. Biophys. Res. Comm. 1995; 216: 582-588Crossref PubMed Scopus (0) Google Scholar) are also found in PSD preparations, as are protein phosphatase 1 (30Dosemeci A Reese T.S Inhibition of endogenous phosphatase in a postsynaptic density fraction allows extensive phosphorylation of the major postsynaptic density protein.J. Neurochem. 1993; 61: 550-555Crossref PubMed Google Scholar) and G proteins (4Aoki C Go C.G Wu K Siekevitz P Light and electron microscopic localization of alpha subunits of GTP-binding proteins, G(o) and Gi, in the cerebral cortex and hippocampus of rat brain.Brain Res. 1992; 596: 189-201Crossref PubMed Google Scholar, 162Wu K Nigam S.K LeDoux M Huang Y.Y Aoki C Siekevitz P Occurrence of the alpha subunits of G proteins in cerebral cortex synaptic membrane and postsynaptic density fractions modulation of ADP-ribosylation by Ca2+/calmodulin.Proc. Natl. Acad. Sci. USA. 1992; 89 (b): 8686-8690Crossref PubMed Google Scholar). A number of these regulatory proteins may be precisely positioned in relation to their regulatory targets. Indeed, several protein kinases are tethered near or within the PSD via specialized adaptor proteins. These adaptors include AKAP (A kinase anchoring protein) 79 and AKAP 150, which anchor type II PKA to the PSD (20Carr D.W Stofko H.R Fraser I.D Cone R.D Scott J.D Localization of the cAMP-dependent protein kinase to the postsynaptic densities by A-kinase anchoring proteins. Characterization of AKAP 79.J. Biol. Chem. 1992; 267: 16816-16823Abstract Full Text PDF PubMed Google Scholar). AKAP 79 also binds calcineurin and is a potent inhibitor of calcineurin function (22Coghlan V.M Perrino B.A Howard M Langeberg L.K Hicks J.B Gallatin W.M Scott J.D Association of protein kinase A and protein phosphatase 2B with a common anchoring protein.Science. 1995; 267: 108-111Crossref PubMed Google Scholar). AKAP 79 binds protein kinase C as well and thus couples three enzymatic functions (89Klauck T.M Faux M.C Labudda K Langeberg L.K Jaken S Scott J.D Coordination of three signaling enzymes by AKAP79, a mammalian scaffold protein.Science. 1996; 271: 1589-1592Crossref PubMed Google Scholar). A 190 kDa CaMKII-binding protein is also found in the PSD fraction (112McNeill R.B Colbran R.J Interaction of autophosphorylated Ca2+/calmodulin-dependent protein kinase II with neuronal cytoskeletal proteins.Characterization of binding to a. 1995; 190-kDa postsynaptic density protein. J. Biol. Chem.: 10043-10049Google Scholar)