title: Association of membrane rafts and postsynaptic density: proteomics, biochemical, and ultrastructural analyses.
abstract: J. Neurochem. (2011) 119, 64-77.
  Postsynaptic membrane rafts are believed to play important roles in synaptic signaling, plasticity, and maintenance. However, their molecular identities remain elusive. Further, how they interact with the well-established signaling specialization, the postsynaptic density (PSD), is poorly understood. We previously detected a number of conventional PSD proteins in detergent-resistant membranes (DRMs). Here, we have performed liquid chromatography coupled with tandem mass spectrometry (LC/MS/MS) analyses on postsynaptic membrane rafts and PSDs. Our comparative analysis identified an extensive overlap of protein components in the two structures. This overlapping could be explained, at least partly, by a physical association of the two structures. Meanwhile, a significant number of proteins displayed biased distributions to either rafts or PSDs, suggesting distinct roles for the two postsynaptic specializations. Using biochemical and electron microscopic methods, we directly detected membrane raft-PSD complexes. In vitro reconstitution experiments indicated that the formation of raft-PSD complexes was not because of the artificial reconstruction of once-solubilized membrane components and PSD structures, supporting that these complexes occurred in vivo. Taking together, our results provide evidence that postsynaptic membrane rafts and PSDs may be physically associated. Such association could be important in postsynaptic signal integration, synaptic function, and maintenance.
authors.affiliation: Department of Neuroplasticity, Institute on Aging and Adaptation, Shinshu University Graduate School of Medicine, Matsumoto, Japan. suzukit@shinshu-u.ac.jp
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Suzuki
authors.forename: Jingping
authors.initials: J
authors.lastname: Zhang
authors.forename: Shoko
authors.initials: S
authors.lastname: Miyazawa
authors.forename: Qian
authors.initials: Q
authors.lastname: Liu
authors.forename: Michael R
authors.initials: MR
authors.lastname: Farzan
authors.forename: Wei-Dong
authors.initials: WD
authors.lastname: Yao
mesh_terms: D000818:Animals; D002499:Centrifugation, Density Gradient; D002784:Cholesterol / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003902:Detergents / Q000737:chemistry; D004591:Electrophoresis, Polyacrylamide Gel; D005677:G(M1) Ganglioside / Q000378:metabolism; D008297:Male; D013058:Mass Spectrometry; D021962:Membrane Microdomains / Q000502:physiology* / Q000648:ultrastructure*; D008854:Microscopy, Electron; D009419:Nerve Tissue Proteins / Q000737:chemistry; D017830:Octoxynol / Q000737:chemistry; D040901:Proteomics; D051381:Rats; D017208:Rats, Wistar; D013569:Synapses / Q000502:physiology* / Q000648:ultrastructure*
chemical_list: D003902:Detergents; D009419:Nerve Tissue Proteins; D005677:G(M1) Ganglioside; D017830:Octoxynol; D002784:Cholesterol