The role of receptor diffusion in the organization of the postsynaptic membrane (original) (raw)

• Peters, A., Palay, S. L. & Webster, H. D. F. The Fine Structure of the Nervous System (Saunders, Philadelphia, Pennsylvania, 1976).
  Google Scholar
• Craig, A. M. & Boudin, H. Molecular heterogeneity of central synapses: afferent and target regulation. Nature Neurosci. 4, 569–578 (2001).
  CAS PubMed Google Scholar
• Nusser, Z. AMPA and NMDA receptors: similarities and differences in their synaptic distribution. Curr. Opin. Neurobiol. 10, 337–341 (2000).
  CAS PubMed Google Scholar
• Kennedy, M. B. Signal-processing machines at the postsynaptic density. Science 290, 750–754 (2000).
  CAS PubMed Google Scholar
• Sheng, M. & Kim, E. Ion channel associated proteins. Curr. Opin. Neurobiol. 6, 602–608 (1996).
  CAS PubMed Google Scholar
• Kornau, H. C., Seeburg, P. H. & Kennedy, M. B. Interaction of ion channels and receptors with PDZ domain proteins. Curr. Opin. Neurobiol. 7, 368–373 (1997).
  CAS PubMed Google Scholar
• Craven, S. E. & Bredt, D. S. PDZ proteins organize synaptic signaling pathways. Cell 93, 495–498 (1998).
  CAS PubMed Google Scholar
• Sheng, M. & Sala, C. PDZ domains and the organization of supramolecular complexes. Annu. Rev. Neurosci. 24, 1–29 (2001).
  CAS PubMed Google Scholar
• Garner, C. C., Nash, J. & Huganir, R. L. PDZ domains in synapse assembly and signalling. Trends Cell Biol. 10, 274–280 (2000).
  CAS PubMed Google Scholar
• Scannevin, R. H. & Huganir, R. L. Postsynaptic organization and regulation of excitatory synapses. Nature Rev. Neurosci. 1, 133–141 (2000).
  CAS Google Scholar
• Moss, S. J. & Smart, T. G. Constructing inhibitory synapses. Nature Rev. Neurosci. 2, 240–250 (2001).
  CAS Google Scholar
• Dingledine, R., Borges, K., Bowie, D. & Traynelis, S. F. The glutamate receptor ion channels. Pharmacol. Rev. 51, 7–61 (1999).
  CAS PubMed Google Scholar
• Pin, J. -P. & Duvoisin, R. The metabotropic glutamate receptors: structure and functions. Neuropharmacology 34, 1–26 (1995).
  CAS PubMed Google Scholar
• Baude, A. et al. The metabotropic glutamate receptors (mGluR1α) is concentrated at perisynaptic membrane of neuronal subpopulations as detected by immunogold reaction. Neuron 11, 771–787 (1993).
  CAS PubMed Google Scholar
• Walikonis, R. S. et al. Identification of proteins in the postsynaptic density fraction by mass spectrometry. J. Neurosci. 20, 4069–4080 (2000).
  CAS PubMed PubMed Central Google Scholar
• Husi, H., Ward, M. A., Choudhary, J. S., Blackstock, W. P. & Grant, S. G. Proteomic analysis of NMDA receptor-adhesion protein signaling complexes. Nature Neurosci. 3, 661–669 (2000).
  CAS PubMed Google Scholar
• Usui, S. et al. Synaptic targeting of PSD-Zip45 (homer 1c) and its involvement in the synaptic accumulation of F-actin. J. Biol. Chem. 278, 10619 - 10628 (2003).
  CAS PubMed Google Scholar
• Xia, J., Zhang, X., Staudinger, J. & Huganir, R. L. Clustering of AMPA receptors by the synaptic PDZ domain-containing protein PICK1. Neuron 22, 179–187 (1999).
  CAS PubMed Google Scholar
• Kim, C. H., Chung, H. J., Lee, H. K. & Huganir, R. L. Interaction of the AMPA receptor subunit GluR2/3 with PDZ domains regulates hippocampal long-term depression. Proc. Natl Acad. Sci. USA 98, 11725–11730 (2001).
  CAS PubMed PubMed Central Google Scholar
• Schnell, E. et al. Direct interactions between PSD-95 and stargazin control synaptic AMPA receptor number. Proc. Natl Acad. Sci. USA 99, 13902–13907 (2002).
  CAS PubMed PubMed Central Google Scholar
• Scheiffele, P., Fan, J., Choih, J., Fetter, R. & Serafini, T. Neuroligin expressed in nonneuronal cells triggers presynaptic development in contacting axons. Cell 101, 657–669 (2000).
  CAS PubMed Google Scholar
• Biederer, T. et al. SynCAM, a synaptic adhesion molecule that drives synapse assembly. Science 297, 1525–1531 (2002).
  CAS PubMed Google Scholar
• Yamagata, M., Weiner, J. A. & Sanes, J. R. Sidekicks: synaptic adhesion molecules that promote lamina-specific connectivity in the retina. Cell 110, 649–660 (2002).
  CAS PubMed Google Scholar
• Fannon, A. M. & Colman, D. R. A model for central synaptic junctional complex formation based on the differential adhesive specificities of the cadherins. Neuron 17, 423–434 (1996).
  CAS PubMed Google Scholar
• Song, J. Y., Ichtchenko, K., Sudhof, T. C. & Brose, N. Neuroligin 1 is a postsynaptic cell-adhesion molecule of excitatory synapses. Proc. Natl Acad. Sci. USA 96, 1100–1105 (1999).
  CAS PubMed PubMed Central Google Scholar
• Irie, M. et al. Binding of neuroligins to PSD-95. Science 277, 1511–1515 (1997). Evidence that adhesion proteins might be involved in the molecular organization of the PSD at glutamatergic synapses.
  CAS PubMed Google Scholar
• Uchida, N., Honjo, Y., Johnson, K. R., Wheelock, M. J. & Takeicji, M. The catenin/cadherin adhesion system is localized in synaptic junctions bordering transmitter release zones. J. Cell Biol. 135, 767–779 (1996).
  CAS PubMed Google Scholar
• Coussen, F. et al. Recruitment of the kainate receptor subunit glutamate receptor 6 by cadherin/catenin complexes. J. Neurosci. 22, 6426–6436 (2002).
  CAS PubMed PubMed Central Google Scholar
• Togashi, H. et al. Cadherin regulates dendritic spine morphogenesis. Neuron 35, 77–89 (2002).
  CAS PubMed Google Scholar
• Dalva, M. et al. EphB receptors interact with NMDA receptors and regulate excitatory synapse formation. Cell 103, 945–956 (2000).
  CAS PubMed Google Scholar
• Allison, D. W., Chervin, A. S., Gelfand, V. I. & Craig, A. M. Postsynaptic scaffolds of excitatory and inhibitory synapses in hippocampal neurons: maintenance of core components independent of actin filaments and microtubules. J. Neurosci. 20, 4545–4554 (2000).
  CAS PubMed PubMed Central Google Scholar
• Allison, D. W., Gelfand, V. I., Spector, I. & Craig, A. M. Role of actin in anchoring postsynaptic receptors in cultured hippocampal neurons: differential attachment of NMDA versus AMPA receptors. J. Neurosci. 18, 2423–2436 (1998).
  CAS PubMed PubMed Central Google Scholar
• Valtschanoff, J. G. & Weinberg, R. J. Laminar organization of the NMDA receptor complex within the postsynaptic density. J. Neurosci. 21, 1211–1217 (2001).
  CAS PubMed PubMed Central Google Scholar
• Triller, A., Cluzeaud, F., Pfeiffer, F., Betz, H. & Korn, H. Distribution of glycine receptors at central synapses: an immunoelectron microscopy study. J. Cell Biol. 101, 683–688 (1985). The first morphological evidence, using immunocytochemistry and electron microscopy, of the postsynaptic accumulation of a receptor for neurotransmitters in the CNS.
  CAS PubMed Google Scholar
• Xiang, S., Nichols, J., Rajagopalan, K. V. & Schindelin, H. The crystal structure of Escherichia coli MoeA and its relationship to the multifunctional protein gephyrin. Structure (Camb.) 9, 299–310 (2001).
  CAS Google Scholar
• Sola, M., Kneussel, M., Heck, I. S., Betz, H. & Weissenhorn, W. X-ray crystal structure of the trimeric N-terminal domain of gephyrin. J. Biol. Chem. 276, 25294–25301 (2001).
  CAS PubMed Google Scholar
• Kneussel, M. & Betz, H. Clustering of inhibitory neurotransmitter receptors at developing postsynaptic sites: the membrane activation model. Trends Neurosci. 23, 429–435 (2000).
  CAS PubMed Google Scholar
• Colin, I., Rostaing, P., Augustin, A. & Triller, A. Localization of components of glycinergic synapses during rat spinal cord development. J. Comp. Neurol. 398, 359–372 (1998).
  CAS PubMed Google Scholar
• Legendre, P. The glycinergic inhibitory synapse. Cell. Mol. Life Sci. 58, 760–793 (2001).
  CAS PubMed Google Scholar
• Fuhrmann, J. et al. Gephyrin interacts with Dynein light chains 1 and 2, components of motor protein complexes. J. Neurosci. 22, 5393–5402 (2002).
  CAS PubMed PubMed Central Google Scholar
• Racca, C., Gardiol, A. & Triller, A. Dendritic postsynaptic localization of glycine receptor α subunit mRNAs. J. Neurosci. 17, 1691–1700 (1997).
  CAS PubMed PubMed Central Google Scholar
• Gardiol, A., Racca, C. & Triller, A. Dendritic and postsynaptic protein synthetic machinery. J. Neurosci. 19, 168–179 (1999).
  CAS PubMed PubMed Central Google Scholar
• Benson, D. L. & Tanaka, H. N-cadherin redistribution during synaptogenesis in hippocampal neurons. J. Neurosci. 18, 6892–6904 (1998).
  CAS PubMed PubMed Central Google Scholar
• Kirsch, J. & Betz, H. The postsynaptic localization of the glycine receptor-associated protein gephyrin is regulated by the cytoskeleton. J. Neurosci. 15, 4148–4156 (1995).
  CAS PubMed PubMed Central Google Scholar
• McGee, A. W. et al. PSD-93 knock-out mice reveal that neuronal MAGUKs are not required for development or function of parallel fiber synapses in cerebellum. J. Neurosci. 21, 3085–3091 (2001).
  CAS PubMed PubMed Central Google Scholar
• Kneussel, M. et al. Gephyrin-independent clustering of postsynaptic GABAA receptor subtypes. Mol. Cell. Neurosci. 17, 973–982 (2001).
  CAS PubMed Google Scholar
• Axelrod, D. et al. Lateral motion of fluorescently labeled acetylcholine receptors in membranes of developing muscle fibers. Proc. Natl Acad. Sci. USA 73, 4594–4598 (1976). The first use of FRAP to demonstrate that a membrane receptor, AChR, can be mobile or immobile in the cell plasma membrane.
  CAS PubMed PubMed Central Google Scholar
• Young, S. H. & Poo, M. M. Rapid lateral diffusion of extrajunctional acetylcholine receptors in the developing muscle membrane of Xenopus tadpole. J. Neurosci. 3, 225–231 (1983). The initial proposal that acetylcholine receptors could aggregate at neuromuscular junctions by diffusing from perijunctional to junctional zones through a 'diffusion-trap' mechanism.
  CAS PubMed PubMed Central Google Scholar
• Rao, A., Kim, E., Sheng, M. & Craig, A. M. Heterogeneity in the molecular composition of excitatory postsynaptic sites during development of hippocampal neurons in culture. J. Neurosci. 18, 1217–1229 (1998).
  CAS PubMed PubMed Central Google Scholar
• Rousselet, A., Cartaud, J., Devaux, P. F. & Changeux, J. P. The rotational diffusion of the acetylcholine receptor in Torpeda marmorata membrane fragments studied with a spin-labelled α-toxin: importance of the 43 000 protein(s). Embo J. 1, 439–445 (1982).
  CAS PubMed PubMed Central Google Scholar
• Garner, C. C., Zhai, R. G., Gundelfinger, E. D. & Ziv, N. E. Molecular mechanisms of CNS synaptogenesis. Trends Neurosci. 25, 243–251 (2002).
  CAS PubMed Google Scholar
• Mammen, A. L., Huganir, R. L. & O'Brien, R. J. Redistribution and stabilization of cell surface glutamate receptors during synapse formation. J. Neurosci. 17, 7351–7358 (1997).
  CAS PubMed PubMed Central Google Scholar
• Cottrell, J. R., Dube, G. R., Egles, C. & Liu, G. Distribution, density, and clustering of functional glutamate receptors before and after synaptogenesis in hippocampal neurons. J. Neurophysiol. 84, 1573–1587 (2000).
  CAS PubMed Google Scholar
• Washbourne, P., Bennett, J. E. & McAllister, A. K. Rapid recruitment of NMDA receptor transport packets to nascent synapses. Nature Neurosci. 5, 751–759 (2002).
  CAS PubMed Google Scholar
• O'Brien, R. J. et al. Synaptic clustering of AMPA receptors by the extracellular immediate-early gene product Narp. Neuron 23, 309–323 (1999).
  CAS PubMed Google Scholar
• Kirsch, J., Wolters, I., Triller, A. & Betz, H. Gephyrin antisense oligonucleotides prevent glycine receptor clustering in spinal neurons. Nature 366, 745–748 (1993).
  CAS PubMed Google Scholar
• Kirsch, J. & Betz, H. Glycine-receptor activation is required for receptor clustering in spinal neurons. Nature 392, 717–720 (1998).
  CAS PubMed Google Scholar
• Lévi, S., Vannier, C. & Triller, A. Strychnine-sensitive stabilization of postsynaptic glycine receptor clusters. J. Cell Sci. 111, 335–345 (1998). References 57 and 58 establish, using a competitive antagonist, that the activation of the glycine receptor is necessary for its postsynaptic accumulation during development.
  PubMed Google Scholar
• Rasmussen, H., Rasmussen, T., Triller, A. & Vannier, C. Strychnine-blocked glycine receptor is removed from synapses by a shift in insertion/degradation equilibrium. Mol. Cell. Neurosci. 19, 201–215 (2002).
  CAS PubMed Google Scholar
• Grutzendler, J., Kasthuri, N. & Gan, W. Long-term dendritic spine stability in the adult cortex. Nature 420, 812–816 (2002).
  CAS PubMed Google Scholar
• Trachtenberg, J. T. et al. Long-term in vivo imaging of experience-dependent synaptic plasticity in adult cortex. Nature 420, 788–794 (2002).
  CAS PubMed Google Scholar
• Akaaboune, M., Culican, S. M., Turney, S. G. & Lichtman, J. W. Rapid and reversible effects of activity on acetylcholine receptor density at the neuromuscular junction in vivo. Science 286, 503–507 (1999).
  CAS PubMed Google Scholar
• Akaaboune, M., Grady, R. M., Turney, S., Sanes, J. R. & Lichtman, J. W. Neurotransmitter receptor dynamics studied in vivo by reversible photo-unbinding of fluorescent ligands. Neuron 34, 865–876 (2002). A very elegant study (with reference 62) using quantitative fluorescence imaging in vivo to demonstrate that receptors are lost rapidly from the neuromuscular postsynaptic junctional area when synaptic activity is blocked, and that this effect is reversible when neurotransmission is restored.
  CAS PubMed Google Scholar
• Carroll, R. C., Beattie, E. C., von Zastrow, M. & Malenka, R. C. Role of ampa receptor endocytosis in synaptic plasticity. Nature Rev. Neurosci. 2, 315–324 (2001).
  CAS Google Scholar
• Barry, M. F. & Ziff, E. B. Receptor trafficking and the plasticity of excitatory synapses. Curr. Opin. Neurobiol. 12, 279–286 (2002).
  CAS PubMed Google Scholar
• Malinow, R. & Malenka, R. C. AMPA receptor trafficking and synaptic plasticity. Annu. Rev. Neurosci. 25, 103–126 (2002).
  CAS PubMed Google Scholar
• Ehlers, M. D. Reinsertion or degradation of AMPA receptors determined by activity-dependent endocytic sorting. Neuron 28, 511–525 (2000).
  CAS PubMed Google Scholar
• Lin, J. W. et al. Distinct molecular mechanisms and divergent endocytotic pathways of AMPA receptor internalization. Nature Neurosci. 3, 1282–1290 (2000).
  CAS PubMed Google Scholar
• Noel, J. et al. Surface expression of AMPA receptors in hippocampal neurons is regulated by an NSF-dependent mechanism. Neuron 23, 365–376 (1999).
  CAS PubMed Google Scholar
• Nishimune, A. et al. NSF binding to GluR2 regulates synaptic transmission. Neuron 21, 87–97 (1998).
  CAS PubMed Google Scholar
• Song, I. et al. Interaction of the N-ethylmaleimide-sensitive factor with AMPA receptors. Neuron 21, 393–400 (1998).
  CAS PubMed Google Scholar
• Lee, S. H., Liu, L., Wang, Y. T. & Sheng, M. Clathrin adaptor AP2 and NSF interact with overlapping sites of GluR2 and play distinct roles in AMPA receptor trafficking and hippocampal LTD. Neuron 36, 661–674 (2002).
  CAS PubMed Google Scholar
• Okabe, S., Kim, H. D., Miwa, A., Kuriu, T. & Okado, H. Continual remodeling of postsynaptic density and its regulation by synaptic activity. Nature Neurosci. 2, 804–811 (1999).
  CAS PubMed Google Scholar
• Barnes, E. M. Jr. Intracellular trafficking of GABAA receptors. Life Sci. 66, 1063–1070 (2000).
  CAS PubMed Google Scholar
• Blanpied, T. A., Scott, D. B. & Ehlers, M. D. Dynamics and regulation of clathrin coats at specialized endocytic zones of dendrites and spines. Neuron 36, 435–449 (2002). A study that established that endocytosis occurs at the edge of postsynaptic densities or further away at the extrasynaptic plasma membrane.
  CAS PubMed Google Scholar
• Rosenberg, M., Meier, J., Triller, A. & Vannier, C. Dynamics of glycine receptor insertion in the neuronal plasma membrane. J. Neurosci. 21, 5036–5044 (2001).
  CAS PubMed PubMed Central Google Scholar
• Passafaro, M., Piech, V. & Sheng, M. Subunit-specific temporal and spatial patterns of AMPA receptor exocytosis in hippocampal neurons. Nature Neurosci. 4, 917–926 (2001). In references 76 and 77, cleavable tags were used to monitor insertion and diffusion of receptors in the plasma membrane. Reference 76 demonstrated that glycine receptors are inserted at extrasynaptic sites and diffuse in the membrane prior to their accumulation at synapses. Reference 77 established that the rate of accumulation of AMPA receptors at synapses depends on their subunit composition.
  CAS PubMed Google Scholar
• Carroll, R. C. & Zukin, R. S. NMDA-receptor trafficking and targeting: implications for synaptic transmission and plasticity. Trends Neurosci. 25, 571–577 (2002).
  CAS PubMed Google Scholar
• Tovar, K. R. & Westbrook, G. L. Mobile NMDA receptors at hippocampal synapses. Neuron 34, 255–264 (2002). An elegant electrophysiological and pharmacological study indicating that NMDARs move laterally between synaptic and extrasynaptic pools, and providing evidence for a dynamic organization of NMDARs in the postsynaptic membrane.
  CAS PubMed Google Scholar
• Sheng, M. & Kim, M. J. Postsynaptic signaling and plasticity mechanisms. Science 298, 776–780 (2002).
  CAS PubMed Google Scholar
• Barria, A., Muller, D., Derkach, V., Griffith, L. C. & Soderling, T. R. Regulatory phosphorylation of AMPA-type glutamate receptors by CaM-KII during long-term potentiation. Science 276, 2042–2045 (1997).
  CAS PubMed Google Scholar
• Kameyama, K., Lee, H. K., Bear, M. F. & Huganir, R. L. Involvement of a postsynaptic protein kinase A substrate in the expression of homosynaptic long-term depression. Neuron 21, 1163–1175 (1998).
  CAS PubMed Google Scholar
• Luthi, A. et al. Hippocampal LTD expression involves a pool of AMPARs regulated by the NSF–GluR2 interaction. Neuron 24, 389–399 (1999).
  CAS PubMed Google Scholar
• Wang, Y. T. & Linden, D. J. Expression of cerebellar long-term depression requires postsynaptic clathrin-mediated endocytosis. Neuron 25, 635–647 (2000).
  CAS PubMed Google Scholar
• Carroll, R. C., Lissin, D. V., von Zastrow, M., Nicoll, R. A. & Malenka, R. C. Rapid redistribution of glutamate receptors contributes to long-term depression in hippocampal cultures. Nature Neurosci. 2, 454–460 (1999).
  CAS PubMed Google Scholar
• Zhou, Q., Xiao, M. & Nicoll, R. A. Contribution of cytoskeleton to the internalization of AMPA receptors. Proc. Natl Acad. Sci. USA 98, 1261–1266 (2001).
  CAS PubMed PubMed Central Google Scholar
• Chen, L. et al. Stargazin regulates synaptic targeting of AMPA receptors by two distinct mechanisms. Nature 408, 936–943 (2000). Physiological, morphological and biochemical evidence that stargazin, a protein that interacts with both AMPAR subunits and the synaptic PDZ protein (PSD-95), is essential for delivering functional AMPARs to synapses. This phenomenon probably occurs through lateral diffusion (see reference 20); disrupting the stargazin–PSD-95 interaction decreases the amount of synaptic AMPARs and increases extrasynaptic AMPARs.
  CAS PubMed Google Scholar
• El-Husseini Ael, D. et al. Synaptic strength regulated by palmitate cycling on PSD-95. Cell 108, 849–863 (2002).
  Google Scholar
• Singer, S. J. & Nicolson, G. L. The fluid mosaic model of the structure of cell membranes. Science 175, 720–731 (1972). The seminal paper proposing that biological membranes are a two-dimensional oriented solution of integral proteins embedded in a viscous phospholipid bilayer.
  CAS PubMed Google Scholar
• Frye, L. D. & Edidin, M. The rapid intermixing of cell surface antigens after formation of mouse–human heterokaryons. J. Cell Sci. 7, 319–335 (1970).
  CAS PubMed Google Scholar
• Axelrod, D., Koppel, D. E., Schlessinger, J., Elson, E. & Webb, W. W. Mobility measurement by analysis of fluorescence photobleaching recovery kinetics. Biophys. J. 16, 1055–1069 (1976).
  CAS PubMed PubMed Central Google Scholar
• Saxton, M. J. & Jacobson, K. Single-particle tracking: applications to membrane dynamics. Annu. Rev. Biophys. Biomol. Struct. 26, 373–399 (1997).
  CAS PubMed Google Scholar
• Jacobson, K., Sheets, E. D. & Simson, R. Revisiting the fluid mosaic model of membranes. Science 268, 1441–1442 (1995).
  CAS PubMed Google Scholar
• Simson, R. et al. Structural mosaicism on the submicron scale in the plasma membrane. Biophys. J. 74, 297–308 (1998).
  CAS PubMed PubMed Central Google Scholar
• Edidin, M., Kuo, S. C. & Sheetz, M. P. Lateral movements of membrane glycoproteins restricted by dynamic cytoplasmic barriers. Science 254, 1379–1382 (1991).
  CAS PubMed Google Scholar
• Sako, Y. & Kusumi, A. Barriers for lateral diffusion of transferrin receptor in the plasma membrane as characterized by receptor dragging by laser tweezers: fence versus tether. J. Cell Biol. 129, 1559–1574 (1995).
  CAS PubMed Google Scholar
• Salome, L., Cazeils, J. L., Lopez, A. & Tocanne, J. F. Characterization of membrane domains by FRAP experiments at variable observation areas. Eur. Biophys. J. 27, 391–402 (1998).
  CAS PubMed Google Scholar
• Edidin, M., Zuniga, M. C. & Sheetz, M. P. Truncation mutants define and locate cytoplasmic barriers to lateral mobility of membrane glycoproteins. Proc. Natl Acad. Sci. USA 91, 3378–3382 (1994).
  CAS PubMed PubMed Central Google Scholar
• Kusumi, A., Sako, Y. & Yamamoto, M. Confined lateral diffusion of membrane receptors as studied by single particle tracking (nanovid microscopy). Effects of calcium-induced differentiation in cultured epithelial cells. Biophys. J. 65, 2021–2040 (1993). Using single particle tracking, references 96 and 99 established that the movements of some membrane proteins are confined within submicrometre-sized domains by the lattice of membrane-associated cytoskeleton, leading to the proposal of the cytoskeleton-fence model.
  CAS PubMed PubMed Central Google Scholar
• Kusumi, A. & Sako, Y. Cell surface organization by the membrane skeleton. Curr. Opin. Cell Biol. 8, 566–574 (1996).
  CAS PubMed Google Scholar
• Edidin, M. Shrinking patches and slippery rafts: scales of domains in the plasma membrane. Trends Cell Biol. 11, 492–496 (2001).
  CAS PubMed Google Scholar
• Fujiwara, T., Ritchie, K., Murakoshi, H., Jacobson, K. & Kusumi, A. Phospholipids undergo hop diffusion in compartmentalized cell membrane. J. Cell Biol. 157, 1071–1081 (2002).
  CAS PubMed PubMed Central Google Scholar
• Sheets, E. D., Lee, G. M., Simson, R. & Jacobson, K. Transient confinement of a glycosylphosphatidylinositol-anchored protein in the plasma membrane. Biochemistry 36, 12449–12458 (1997).
  CAS PubMed Google Scholar
• Vrljic, M., Nishimura, S. Y., Brasselet, S., Moerner, W. E. & McConnell, H. M. Translational diffusion of individual class II MHC membrane proteins in cells. Biophys. J. 83, 2681–2692 (2002).
  CAS PubMed PubMed Central Google Scholar
• Daumas, F. et al. Confined diffusion without fences of a G protein coupled receptor as revealed by single particle tracking. Biophys. J. 84, 356–366 (2003).
  CAS PubMed PubMed Central Google Scholar
• Saxton, M. J. Anomalous diffusion due to obstacles: a Monte Carlo study. Biophys. J. 66, 394–401 (1994).
  CAS PubMed PubMed Central Google Scholar
• Simons, K. & Ikonen, E. Functional rafts in cell membranes. Nature 387, 569–572 (1997).
  CAS PubMed Google Scholar
• Pralle, A., Keller, P., Florin, E. L., Simons, K. & Horber, J. K. Sphingolipid-cholesterol rafts diffuse as small entities in the plasma membrane of mammalian cells. J. Cell Biol. 148, 997–1008 (2000).
  CAS PubMed PubMed Central Google Scholar
• Dietrich, C., Yang, B., Fujiwara, T., Kusumi, A. & Jacobson, K. Relationship of lipid rafts to transient confinement zones detected by single particle tracking. Biophys. J. 82, 274–284 (2002).
  CAS PubMed PubMed Central Google Scholar
• Sonnleitner, A., Schutz, G. J. & Schmidt, T. Free brownian motion of individual lipid molecules in biomembranes. Biophys. J. 77, 2638–2642 (1999).
  CAS PubMed PubMed Central Google Scholar
• Schmidt, T., Schutz, G. J., Baumgartner, W., Gruber, H. J. & Schindler, H. Imaging of single molecule diffusion. Proc. Natl Acad. Sci. USA 93, 2926–2929 (1996).
  CAS PubMed PubMed Central Google Scholar
• Winckler, B., Forscher, P. & Mellman, I. A diffusion barrier maintains distribution of membrane proteins in polarized neurons. Nature 397, 698–701 (1999). The demonstration that in neurons, the axon hillock is a specialized domain restricting the diffusion of certain membrane proteins. The authors propose that this barrier contributes to the polarized distribution of membrane proteins between the axonal and the somatodendritic compartments.
  CAS PubMed Google Scholar
• Garrido, J. J. et al. Identification of an axonal determinant in the C-terminus of the sodium channel Nav1. 2. Embo J. 20, 5950–5961 (2001).
  CAS PubMed PubMed Central Google Scholar
• el-Husseini Ael, D. & Bredt, D. S. Protein palmitoylation: a regulator of neuronal development and function. Nature Rev. Neurosci. 3, 791–802 (2002).
  Google Scholar
• Suzuki, T. et al. Biochemical evidence for localization of AMPA-type glutamate receptor subunits in the dendritic raft. Brain Res. Mol. Brain Res. 89, 20–28 (2001).
  CAS PubMed Google Scholar
• Bruses, J. L., Chauvet, N. & Rutishauser, U. Membrane lipid rafts are necessary for the maintenance of the α7 nicotinic acetylcholine receptor in somatic spines of ciliary neurons. J. Neurosci. 21, 504–512 (2001).
  CAS PubMed PubMed Central Google Scholar
• Lippincott-Schwartz, J., Snapp, E. & Kenworthy, A. Studying protein dynamics in living cells. Nature Rev. Mol. Cell Biol. 2, 444–456 (2001).
  CAS Google Scholar
• Kornau, H. C., Schenker, L. T., Kennedy, M. B. & Seeburg, P. H. Domain interaction between NMDA receptor subunits and the postsynaptic density protein PSD-95. Science 269, 1737–1740 (1995).
  CAS PubMed Google Scholar
• Naisbitt, S. et al. Shank, a novel family of postsynaptic density proteins that binds to the NMDA receptor/PSD-95/GKAP complex and cortactin. Neuron 23, 569–582 (1999).
  CAS PubMed Google Scholar
• Sergé, A., Fourgeaud, L., Hémar, A. & Choquet, D. Receptor activation and homer differentially control the lateral mobility of mGluR5 in the neuronal membrane. J. Neurosci. 22, 3910–3920 (2002).
  PubMed PubMed Central Google Scholar
• Meier, J., Meunier-Durmort, C., Forest, C., Triller, A. & Vannier, C. Formation of glycine receptor clusters and their accumulation at synapses. J. Cell Sci. 113, 2783–2795 (2000).
  CAS PubMed Google Scholar
• Borgdorff, A. & Choquet, D. Regulation of AMPA receptor lateral movement. Nature 417, 649–653 (2002).
  CAS PubMed Google Scholar
• Meier, J., Vannier, C., Sergé, A., Triller, A. & Choquet, D. Fast and reversible trapping of surface glycine receptors by gephyrin. Nature Neurosci. 4, 253–260 (2001). Real-time receptor movements were visualized and analyzed for the first time in references 123 and 122 for AMPA and glycine receptors, respectively. It was established that interactions of receptors with scaffolding proteins are reversible. Furthermore, basal neuronal activity and intracellular calcium levels in synaptically connected neurons could also control AMPA receptor movement.
  CAS PubMed Google Scholar
• Kucik, D. F., Elson, E. L. & Sheetz, M. P. Weak dependence of mobility of membrane protein aggregates on aggregate size supports a viscous model of retardation of diffusion. Biophys. J. 76, 314–322 (1999).
  CAS PubMed PubMed Central Google Scholar
• Anderson, R. G. & Jacobson, K. A role for lipid shells in targeting proteins to caveolae, rafts, and other lipid domains. Science 296, 1821–1825 (2002).
  CAS PubMed Google Scholar
• Saffman, P. G. & Delbruck, M. Brownian motion in biological membranes. Proc. Natl Acad. Sci. USA 72, 3111–3113 (1975). A theoretical calculation of the dependence of diffusion coefficients on object size in biological membranes.
  CAS PubMed PubMed Central Google Scholar
• Patterson, G. H. & Lippincott-Schwartz, J. A photoactivatable GFP for selective photolabeling of proteins and cells. Science 297, 1873–1877 (2002).
  CAS PubMed Google Scholar
• Schnapp, B. J., Gelles, J. & Sheetz, M. P. Nanometer-scale measurements using video light microscopy. Cell Motil. Cytoskeleton 10, 47–53 (1988).
  CAS PubMed Google Scholar
• Geerts, H. et al. Nanovid tracking: a new automatic method for the study of mobility in living cells based on colloidal gold and video microscopy. Biophys. J. 52, 775–782 (1987).
  CAS PubMed PubMed Central Google Scholar
• Boyer, D., Tamarat, P., Maali, A., Lounis, B. & Orrit, M. Photothermal imaging of nanometer-sized metal particles among scatterers. Science 297, 1160–1163 (2002).
  CAS PubMed Google Scholar