Stargazin attenuates intracellular polyamine block of calcium-permeable AMPA receptors

Endogenous polyamines profoundly affect the activity of various ion channels, including that of calcium-permeable AMPA-type glutamate receptors (CP-AMPARs). Here we show that stargazin, a transmembrane AMPAR regulatory protein (TARP) known to influence transport, gating and desensitization of AMPARs, greatly reduces block of CP-AMPARs by intracellular polyamines. By decreasing CP-AMPAR affinity for cytoplasmic polyamines, stargazin enhances the charge transfer following single glutamate applications and eliminates the frequency-dependent facilitation seen with repeated applications. In cerebellar stellate cells, which express both synaptic CP-AMPARs and stargazin, we found that the rectification and unitary conductance of channels underlying excitatory postsynaptic currents were matched by those of recombinant AMPARs only when the latter were associated with stargazin. Taken together, our observations establish modulatory actions of stargazin that are specific to CP-AMPARs, and suggest that during synaptic transmission the activity of such receptors, and thus calcium influx, is fundamentally changed by TARPs.

[1]  Daniel Choquet,et al.  The Interaction between Stargazin and PSD-95 Regulates AMPA Receptor Surface Trafficking , 2007, Neuron.

[2]  Mark Farrant,et al.  Regulation of Ca2+-permeable AMPA receptors: synaptic plasticity and beyond , 2006, Current Opinion in Neurobiology.

[3]  Bernardo L Sabatini,et al.  Synapse-specific plasticity and compartmentalized signaling in cerebellar stellate cells , 2006, Nature Neuroscience.

[4]  R. Silver,et al.  Estimated conductance of glutamate receptor channels activated during EPSCs at the cerebellar mossy fiber-granule cell synapse , 1993, Neuron.

[5]  R. Petralia,et al.  Glutamate receptor subunit 2‐selective antibody shows a differential distribution of calcium‐impermeable AMPA receptors among populations of neurons , 1997, The Journal of comparative neurology.

[6]  J D Clements,et al.  Detection of spontaneous synaptic events with an optimally scaled template. , 1997, Biophysical journal.

[7]  A. Buchan,et al.  Hypothermia rescues hippocampal CA1 neurons and attenuates down-regulation of the AMPA receptor GluR2 subunit after forebrain ischemia , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[8]  Masahiko Watanabe,et al.  A novel action of stargazin as an enhancer of AMPA receptor activity , 2004, Neuroscience Research.

[9]  H. Adesnik,et al.  Stargazin modulates AMPA receptor gating and trafficking by distinct domains , 2005, Nature.

[10]  J. Black,et al.  Biochemical and anatomical evidence for specialized voltage-dependent calcium channel γ isoform expression in the epileptic and ataxic mouse, stargazer , 2001, Neuroscience.

[11]  Wade G. Regehr,et al.  Local Interneurons Regulate Synaptic Strength by Retrograde Release of Endocannabinoids , 2006, The Journal of Neuroscience.

[12]  P. Seeburg,et al.  Regulation of ion channel/neurotransmitter receptor function by RNA editing , 2003, Current Opinion in Neurobiology.

[13]  P. Jonas,et al.  Block of native Ca(2+)‐permeable AMPA receptors in rat brain by intracellular polyamines generates double rectification. , 1995, The Journal of physiology.

[14]  J. Huguenard,et al.  Polyamines modulate AMPA receptor-dependent synaptic responses in immature layer v pyramidal neurons. , 2005, Journal of neurophysiology.

[15]  C. McBain,et al.  Interneuron Diversity series: Containing the detonation – feedforward inhibition in the CA3 hippocampus , 2003, Trends in Neurosciences.

[16]  J. Weiss,et al.  Calcium-permeable AMPA channels in neurodegenerative disease and ischemia , 2006, Current Opinion in Neurobiology.

[17]  Sunjeev K Kamboj,et al.  Intracellular spermine confers rectification on rat calcium‐permeable AMPA and kainate receptors. , 1995, The Journal of physiology.

[18]  C. Körber,et al.  Electrophysiological Properties of AMPA Receptors Are Differentially Modulated Depending on the Associated Member of the TARP Family , 2007, The Journal of Neuroscience.

[19]  G. Collingridge,et al.  Transient incorporation of native GluR2-lacking AMPA receptors during hippocampal long-term potentiation , 2006, Nature Neuroscience.

[20]  D. Feldmeyer,et al.  Neurological dysfunctions in mice expressing different levels of the Q/R site–unedited AMPAR subunit GluR–B , 1999, Nature Neuroscience.

[21]  K. Partin,et al.  Different Domains of the AMPA Receptor Direct Stargazin-mediated Trafficking and Stargazin-mediated Modulation of Kinetics* , 2006, Journal of Biological Chemistry.

[22]  Peter Jonas,et al.  The Time Course of Signaling at Central Glutamatergic Synapses. , 2000, News in physiological sciences : an international journal of physiology produced jointly by the International Union of Physiological Sciences and the American Physiological Society.

[23]  M. Mayer,et al.  Inward rectification of both AMPA and kainate subtype glutamate receptors generated by polyamine-mediated ion channel block , 1995, Neuron.

[24]  B. Sakmann,et al.  Action of brief pulses of glutamate on AMPA/kainate receptors in patches from different neurones of rat hippocampal slices. , 1992, The Journal of physiology.

[25]  M. Mayer,et al.  The role of hydrophobic interactions in binding of polyamines to non NMDA receptor ion channels , 1998, Neuropharmacology.

[26]  R. Nicoll,et al.  Auxiliary Subunits Assist AMPA-Type Glutamate Receptors , 2006, Science.

[27]  Andrei Rozov,et al.  Polyamine-dependent facilitation of postsynaptic AMPA receptors counteracts paired-pulse depression , 1999, Nature.

[28]  B. Clark,et al.  Activity-Dependent Recruitment of Extrasynaptic NMDA Receptor Activation at an AMPA Receptor-Only Synapse , 2002, The Journal of Neuroscience.

[29]  F. Schweizer,et al.  Synapses , 2022, European Lisp Symposium.

[30]  H. Adesnik,et al.  Conservation of Glutamate Receptor 2-Containing AMPA Receptors during Long-Term Potentiation , 2007, The Journal of Neuroscience.

[31]  D. K. Patneau,et al.  Stargazin Modulates Native AMPA Receptor Functional Properties by Two Distinct Mechanisms , 2005, The Journal of Neuroscience.

[32]  Dane M. Chetkovich,et al.  Stargazin regulates synaptic targeting of AMPA receptors by two distinct mechanisms , 2000, Nature.

[33]  F. Sigworth.  The variance of sodium current fluctuations at the node of Ranvier , 1980, The Journal of physiology.

[34]  E. Ziff.  TARPs and the AMPA Receptor Trafficking Paradox , 2007, Neuron.

[35]  R. Nicoll,et al.  Dynamic Interaction of Stargazin-like TARPs with Cycling AMPA Receptors at Synapses , 2004, Science.

[36]  Ichiro Kanazawa,et al.  Glutamate receptors: RNA editing and death of motor neurons , 2004, Nature.

[37]  P. Jonas,et al.  TwoB or not twoB: differential transmission at glutamatergic mossy fiber–interneuron synapses in the hippocampus , 2002, Trends in Neurosciences.

[38]  S. Cull-Candy,et al.  Single-Channel Properties of Recombinant AMPA Receptors Depend on RNA Editing, Splice Variation, and Subunit Composition , 1997, The Journal of Neuroscience.

[39]  P. Osten,et al.  Stargazin Reduces Desensitization and Slows Deactivation of the AMPA-Type Glutamate Receptors , 2005, The Journal of Neuroscience.

[40]  B. Sakmann,et al.  Relative abundance of subunit mRNAs determines gating and Ca2+ permeability of AMPA receptors in principal neurons and interneurons in rat CNS , 1995, Neuron.

[41]  H. Cline,et al.  Visually Driven Modulation of Glutamatergic Synaptic Transmission Is Mediated by the Regulation of Intracellular Polyamines , 2002, Neuron.

[42]  Kevin J. Tracey,et al.  Synaptic activity at calcium-permeable AMPA receptors induces a switch in receptor subtype , 2022 .

[43]  N. Burnashev,et al.  Facilitation of currents through rat Ca2+‐permeable AMPA receptor channels by activity‐dependent relief from polyamine block , 1998, The Journal of physiology.

[44]  S. Cull-Candy,et al.  Subunit interaction with PICK and GRIP controls Ca2+ permeability of AMPARs at cerebellar synapses , 2005, Nature Neuroscience.

[45]  B. Sakmann,et al.  A family of AMPA-selective glutamate receptors. , 1990, Science.

[46]  R. Huganir,et al.  Calcium-Permeable AMPA Receptor Plasticity Is Mediated by Subunit-Specific Interactions with PICK1 and NSF , 2005, Neuron.

[47]  D. Bowie,et al.  Activity-Dependent Modulation of Glutamate Receptors by Polyamines , 1998, The Journal of Neuroscience.

[48]  C. McBain,et al.  Distinct NMDA Receptors Provide Differential Modes of Transmission at Mossy Fiber-Interneuron Synapses , 2002, Neuron.

[49]  R. Nicoll,et al.  Functional studies and distribution define a family of transmembrane AMPA receptor regulatory proteins , 2003, The Journal of cell biology.

[50]  C. Hölscher.  Synaptic plasticity and learning and memory: LTP and beyond , 1999, Journal of neuroscience research.

[51]  A. Dolphin,et al.  Human neuronal stargazin-like proteins, γ2, γ3 and γ4; an investigation of their specific localization in human brain and their influence on CaV2.1 voltage-dependent calcium channels expressed in Xenopus oocytes. , 2003, BMC Neuroscience.

[52]  C. Lüscher,et al.  Cocaine triggered AMPA receptor redistribution is reversed in vivo by mGluR-dependent long-term depression , 2006, Nature Neuroscience.