The Expanding Social Network of Ionotropic Glutamate Receptors: TARPs and Other Transmembrane Auxiliary Subunits

Overview

Journal Neuron

Publisher Cell Press

Specialty Neurology

Date 2011 Apr 28

PMID 21521608

Citations 243

Authors

Alexander C Jackson

Roger A Nicoll

Affiliations

Soon will be listed here.

Abstract

Ionotropic glutamate receptors (iGluRs) underlie rapid, excitatory synaptic signaling throughout the CNS. After years of intense research, our picture of iGluRs has evolved from them being companionless in the postsynaptic membrane to them being the hub of dynamic supramolecular signaling complexes, interacting with an ever-expanding litany of other proteins that regulate their trafficking, scaffolding, stability, signaling, and turnover. In particular, the discovery that transmembrane AMPA receptor regulatory proteins (TARPs) are AMPA receptor auxiliary subunits that are critical determinants of their trafficking, gating, and pharmacology has changed the way we think about iGluR function. Recently, a number of novel transmembrane proteins have been uncovered that may also serve as iGluR auxiliary proteins. Here we review pivotal developments in our understanding of the role of TARPs in AMPA receptor trafficking and gating, and provide an overview of how newly discovered transmembrane proteins expand our view of iGluR function in the CNS.

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References

Yamazaki M, Fukaya M, Hashimoto K, Yamasaki M, Tsujita M, Itakura M . TARPs gamma-2 and gamma-7 are essential for AMPA receptor expression in the cerebellum. Eur J Neurosci. 2010; 31(12):2204-20. DOI: 10.1111/j.1460-9568.2010.07254.x. View

Jonas P, Spruston N . Mechanisms shaping glutamate-mediated excitatory postsynaptic currents in the CNS. Curr Opin Neurobiol. 1994; 4(3):366-72. DOI: 10.1016/0959-4388(94)90098-1. View

Kerchner G, Nicoll R . Silent synapses and the emergence of a postsynaptic mechanism for LTP. Nat Rev Neurosci. 2008; 9(11):813-25. PMC: 2819160. DOI: 10.1038/nrn2501. View

Kessels H, Kopec C, Klein M, Malinow R . Roles of stargazin and phosphorylation in the control of AMPA receptor subcellular distribution. Nat Neurosci. 2009; 12(7):888-96. PMC: 3922706. DOI: 10.1038/nn.2340. View

Castillo P, Malenka R, Nicoll R . Kainate receptors mediate a slow postsynaptic current in hippocampal CA3 neurons. Nature. 1997; 388(6638):182-6. DOI: 10.1038/40645. View

Roth S, BARCELO G, Schupbach T . cornichon and the EGF receptor signaling process are necessary for both anterior-posterior and dorsal-ventral pattern formation in Drosophila. Cell. 1995; 81(6):967-78. DOI: 10.1016/0092-8674(95)90016-0. View

Malenka R, Bear M . LTP and LTD: an embarrassment of riches. Neuron. 2004; 44(1):5-21. DOI: 10.1016/j.neuron.2004.09.012. View

Bowie D, Mayer M . Inward rectification of both AMPA and kainate subtype glutamate receptors generated by polyamine-mediated ion channel block. Neuron. 1995; 15(2):453-62. DOI: 10.1016/0896-6273(95)90049-7. View

Fukata Y, Tzingounis A, Trinidad J, Fukata M, Burlingame A, Nicoll R . Molecular constituents of neuronal AMPA receptors. J Cell Biol. 2005; 169(3):399-404. PMC: 2171936. DOI: 10.1083/jcb.200501121. View

10.

Turetsky D, Garringer E, Patneau D . Stargazin modulates native AMPA receptor functional properties by two distinct mechanisms. J Neurosci. 2005; 25(32):7438-48. PMC: 6725298. DOI: 10.1523/JNEUROSCI.1108-05.2005. View

11.

Cokic B, Stein V . Stargazin modulates AMPA receptor antagonism. Neuropharmacology. 2008; 54(7):1062-70. DOI: 10.1016/j.neuropharm.2008.02.012. View

12.

Wollmuth L, Sobolevsky A . Structure and gating of the glutamate receptor ion channel. Trends Neurosci. 2004; 27(6):321-8. DOI: 10.1016/j.tins.2004.04.005. View

13.

Suzuki E, Kessler M, Arai A . The fast kinetics of AMPA GluR3 receptors is selectively modulated by the TARPs gamma 4 and gamma 8. Mol Cell Neurosci. 2008; 38(1):117-23. DOI: 10.1016/j.mcn.2008.01.018. View

14.

Cull-Candy S, Usowicz M . Multiple-conductance channels activated by excitatory amino acids in cerebellar neurons. Nature. 1987; 325(6104):525-8. DOI: 10.1038/325525a0. View

15.

Sager C, Terhag J, Kott S, Hollmann M . C-terminal domains of transmembrane alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptor regulatory proteins not only facilitate trafficking but are major modulators of AMPA receptor function. J Biol Chem. 2009; 284(47):32413-24. PMC: 2781656. DOI: 10.1074/jbc.M109.039891. View

16.

Swanson G, Heinemann S . Heterogeneity of homomeric GluR5 kainate receptor desensitization expressed in HEK293 cells. J Physiol. 1998; 513 ( Pt 3):639-46. PMC: 2231309. DOI: 10.1111/j.1469-7793.1998.639ba.x. View

17.

Bokel C, Dass S, Wilsch-Brauninger M, Roth S . Drosophila Cornichon acts as cargo receptor for ER export of the TGFalpha-like growth factor Gurken. Development. 2006; 133(3):459-70. DOI: 10.1242/dev.02219. View

18.

Koh D, Burnashev N, Jonas P . Block of native Ca(2+)-permeable AMPA receptors in rat brain by intracellular polyamines generates double rectification. J Physiol. 1995; 486 ( Pt 2):305-12. PMC: 1156522. DOI: 10.1113/jphysiol.1995.sp020813. View

19.

Chevaleyre V, Siegelbaum S . Strong CA2 pyramidal neuron synapses define a powerful disynaptic cortico-hippocampal loop. Neuron. 2010; 66(4):560-72. PMC: 2905041. DOI: 10.1016/j.neuron.2010.04.013. View

20.

Letts V, Felix R, Biddlecome G, Arikkath J, Mahaffey C, Valenzuela A . The mouse stargazer gene encodes a neuronal Ca2+-channel gamma subunit. Nat Genet. 1998; 19(4):340-7. DOI: 10.1038/1228. View