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Titolo:
GABA(C) receptor rho subunits are heterogeneously expressed in the human CNS and form homo- and heterooligomers with distinct physical properties
Autore:
Enz, R; Cutting, GR;
Indirizzi:
Johns87opkins Univ, Sch Med, Dept Pediat, Inst Med Genet, Baltimore, MD 212 Johns Hopkins Univ Baltimore MD USA 21287 st Med Genet, Baltimore, MD 212
Titolo Testata:
EUROPEAN JOURNAL OF NEUROSCIENCE
fascicolo: 1, volume: 11, anno: 1999,
pagine: 41 - 50
SICI:
0953-816X(199901)11:1<41:GRRSAH>2.0.ZU;2-Q
Fonte:
ISI
Lingua:
ENG
Soggetto:
GAMMA-AMINOBUTYRIC-ACID; RETINAL BIPOLAR CELLS; XENOPUS OOCYTES; AMINO-ACID; IMMUNOCYTOCHEMICAL LOCALIZATION; C-RECEPTOR; COS CELLS; BICUCULLINE; RAT; IDENTIFICATION;
Keywords:
inactivation profile; ligand-gated ion channel; receptor assembly; retina;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
55
Recensione:
Indirizzi per estratti:
Indirizzo: Cutting, GR Johns87opkins Univ, Sch Med, Dept Pediat, Inst Med Genet, Baltimore, MD 212 Johns Hopkins Univ Baltimore MD USA 21287 , Baltimore, MD 212
Citazione:
R. Enz e G.R. Cutting, "GABA(C) receptor rho subunits are heterogeneously expressed in the human CNS and form homo- and heterooligomers with distinct physical properties", EUR J NEURO, 11(1), 1999, pp. 41-50

Abstract

In the central nervous system, receptors for gamma-aminobutyric acid (GABA) are responsible for inhibitory neurotransmission. Anatomical and electrophysiological studies indicate that GABA(C) receptors are composed of rho subunits. While the rho 1 subunit of various species forms homooligomeric receptors with GABA(C)-like properties, molecular cloning has identified additional rho subunits whose functional role is unclear. By RT-PCR, we demonstrated that rho 1 expression is primarily restricted to the retina, whereas the rho 2 subunit was present in all brain regions tested. Transfection of HEK-293 cells with rho 2 cDNA resulted in GABA-gated whole-cell currents that differed from those mediated by the rho 1 subunit in two respects: maximal amplitude (rho 1:rho 2 approximate to 4:1) and inactivation time course (rho 1:rho 2 approximate to 2:1). Cotransfection of rho 1 and rho 2 cDNA in a 1:1 ratio generated whole-cell currents with large amplitudes characteristic of rho 1 but more rapid inactivation typical for rho 2. This observation suggested formation of heterooligomeric GABA(C) receptors with distinct features. Therefore, we tested the assembly of rho 1 and rho 2 subunits by cotransfecting rho 2 cDNA together with a chimeric rho 1 beta 1 subunit, known to interfere with rho 1 assembly in a dominant-negative fashion. Reduction of rho 2 generated currents correlated with the ratio of chimeric to rho2 cDNA. Secondly, we determined that the picrotoxinin sensitivity of cellstransfected with various ratios of rho 1 and rho 2 cDNA differed from thatexpected of a pure mixture of homooligomeric receptors. The latter two observations support the idea that rho 1 and rho 2 subunits form heterooligomeric GABA(C) receptors in mammalian cells. Together, our results indicate that the presence of both rho subunits enables the formation of heterooligomeric receptors with physical properties distinct from homooligomers, thus increasing the diversity of GABA(C) receptors in the CNS.

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Documento generato il 01/04/20 alle ore 10:35:42