 |
 Previous Article | Next Article 
The Journal of Neuroscience, August 15, 2000, 20(16):5973-5980
The Lurcher Mutation Identifies  2 as an AMPA/Kainate
Receptor-Like Channel That Is Potentiated by Ca2+
Lonnie P.
Wollmuth1,
Thomas
Kuner2, 3,
Claudia
Jatzke1,
Peter H.
Seeburg3,
Nathaniel
Heintz4, and
Jian
Zuo4, 5
1 Department of Neurobiology and Behavior, State
University of New York at Stony Brook, Stony Brook, New York
11794-5230, 2 Department of Neurobiology, Duke University
Medical Center, Durham, North Carolina 27710, 3 Abteilung
Molekulare Neurobiologie, Max-Planck-Institut für medizinische
Forschung, D-69120 Heidelberg, Germany, 4 Laboratory of
Molecular Biology, Howard Hughes Medical Institute, The Rockefeller
University, New York, New York 10021, and 5 Department of
Developmental Neurobiology, St. Jude Children's Research Hospital,
Memphis, Tennessee 38105
Neurodegeneration in Lurcher (Lc) mice results
from constitutive activation of  2, a subunit of ionotropic glutamate
receptors (GluRs) with unknown natural ligands and channel
properties. Homo-oligomeric channels of GluR-2 with the Lurcher
mutation (GluR-2Lc) expressed in human embryonic
kidney 293 cells showed a doubly rectifying current-voltage
relation reminiscent of the block by intracellular polyamines in
AMPA/kainate channels. Similarly, the fraction of the total current
carried by Ca2+ was ~2-3%, comparable with that
found in Ca2+-permeable AMPA/kainate channels.
Currents through GluR-2Lc channels were also
potentiated by extracellular Ca2+ in a biphasic
manner, with maximal potentiation occurring at physiological
concentrations of Ca2+. We examined the functional
role of the Q/R site in GluR-2Lc by replacing
glutamine with arginine. Analogous to AMPA/kainate receptors,
GluR-2Lc(R) channels showed no voltage-dependent
block by intracellular polyamines and were nominally impermeable to
Ca2+. The potentiation by Ca2+,
however, remained intact. Hence, GluR-2Lc
channels are functionally similar to the AMPA/kainate receptor channels, consistent with the high-sequence identity shared by these
subunits within the channel-lining M2 and M3 segments. Furthermore, potentiation by Ca2+ and a permeability to
Ca2+ comparable with that of AMPA/kainate receptors
provide a possible cause for cell death in Lurcher mice and may
contribute to cerebellar long-term depression under physiological conditions.
Key words:
glutamate receptors; 2; Lurcher mutation; polyamine
block; Ca2+ permeability; fractional
Ca2+ currents
Copyright © 2000 Society for Neuroscience 0270-6474/00/20165973-08$05.00/0
This article has been cited by other articles:
|
|
|
|
 
C. Villmann and C.-M. Becker
On the Hypes and Falls in Neuroprotection: Targeting the NMDA Receptor
Neuroscientist,
December 1, 2007;
13(6):
594 - 615.
[Abstract]
[PDF]
|
|
|
|
|
|
|
W. Kakegawa, K. Kohda, and M. Yuzaki
The {delta}2 'ionotropic' glutamate receptor functions as a non-ionotropic receptor to control cerebellar synaptic plasticity
J. Physiol.,
October 1, 2007;
584(1):
89 - 96.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Naur, K. B. Hansen, A. S. Kristensen, S. M. Dravid, D. S. Pickering, L. Olsen, B. Vestergaard, J. Egebjerg, M. Gajhede, S. F. Traynelis, et al.
Ionotropic glutamate-like receptor {delta}2 binds D-serine and glycine
PNAS,
August 28, 2007;
104(35):
14116 - 14121.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Gao, S. F. Maison, X. Wu, K. Hirose, S. M. Jones, I. Bayazitov, Y. Tian, G. Mittleman, D. B. Matthews, S. S. Zakharenko, et al.
Orphan Glutamate Receptor {delta}1 Subunit Required for High-Frequency Hearing
Mol. Cell. Biol.,
June 15, 2007;
27(12):
4500 - 4512.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. Kakegawa, T. Miyazaki, H. Hirai, J. Motohashi, M. Mishina, M. Watanabe, and M. Yuzaki
Ca2+ permeability of the channel pore is not essential for the {delta}2 glutamate receptor to regulate synaptic plasticity and motor coordination
J. Physiol.,
March 15, 2007;
579(3):
729 - 735.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. M. Klein and J. R. Howe
Effects of the Lurcher Mutation on GluR1 Desensitization and Activation Kinetics
J. Neurosci.,
May 26, 2004;
24(21):
4941 - 4951.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Williams, M. Dattilo, T. N. Sabado, K. Kashiwagi, and K. Igarashi.
Pharmacology of delta 2 Glutamate Receptors: Effects of Pentamidine and Protons
J. Pharmacol. Exp. Ther.,
May 1, 2003;
305(2):
740 - 748.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. Lu and S. E. Tsirka
Partial rescue of neural apoptosis in the Lurcher mutant mouse through elimination of tissue plasminogen activator
Development,
March 6, 2003;
129(8):
2043 - 2050.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Ichikawa, T. Miyazaki, M. Kano, T. Hashikawa, H. Tatsumi, K. Sakimura, M. Mishina, Y. Inoue, and M. Watanabe
Distal Extension of Climbing Fiber Territory and Multiple Innervation Caused by Aberrant Wiring to Adjacent Spiny Branchlets in Cerebellar Purkinje Cells Lacking Glutamate Receptor delta 2
J. Neurosci.,
October 1, 2002;
22(19):
8487 - 8503.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. C. Chiu, E. D. Brenner, R. DeSalle, M. N. Nitabach, T. C. Holmes, and G. M. Coruzzi
Phylogenetic and Expression Analysis of the Glutamate-Receptor-Like Gene Family in Arabidopsis thaliana
Mol. Biol. Evol.,
July 1, 2002;
19(7):
1066 - 1082.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Miyagi, T. Yamashita, M. Fukaya, T. Sonoda, T. Okuno, K. Yamada, M. Watanabe, Y. Nagashima, I. Aoki, K. Okuda, et al.
Delphilin: a Novel PDZ and Formin Homology Domain-Containing Protein that Synaptically Colocalizes and Interacts with Glutamate Receptor delta 2 Subunit
J. Neurosci.,
February 1, 2002;
22(3):
803 - 814.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. K. Ghosh, S. Haverkamp, and H. Wassle
Glutamate Receptors in the Rod Pathway of the Mammalian Retina
J. Neurosci.,
November 1, 2001;
21(21):
8636 - 8647.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Jatzke, J. Watanabe, and L. P. Wollmuth
Voltage and concentration dependence of Ca2+ permeability in recombinant glutamate receptor subtypes
J. Physiol.,
January 1, 2002;
538(1):
25 - 39.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
