Marlin-1, a novel RNA-binding protein associates with GABA receptors.
GABA(B) receptors are heterodimeric G protein-coupled receptors that mediate slow synaptic inhibition in the central nervous system. Whereas heterodimerization between GABA(B) receptor GABA(B)R1 and GABA(B)R2 subunits is essential for functional expression, how neurons coordinate the assembly of these critical receptors remains to be established. Here we have identified Marlin-1, a novel GABA(B) receptor-binding protein that associates specifically with the GABA(B)R1 subunit in yeast, tissue culture cells, and neurons. Marlin-1 is expressed in the brain and exhibits a granular distribution in cultured hippocampal neurons. Marlin-1 binds different RNA species including the 3'-untranslated regions of both the GABA(B)R1 and GABA(B)R2 mRNAs in vitro and also associates with RNA in cultured neurons. Inhibition of Marlin-1 expression via small RNA interference technology results in enhanced intracellular levels of the GABA(B)R2 receptor subunit without affecting the level of GABA(B)R1. Together our results suggest that Marlin-1 functions to regulate the cellular levels of GABA(B) R2 subunits, which may have significant effects on the production of functional GABA(B) receptor heterodimers. Therefore, our observations provide an added level of regulation for the control of GABA(B) receptor expression and for the efficacy of inhibitory synaptic transmission.
Couve
Andrés
A
Department of Pharmacology, University College London, Gower Street, London WC1E 6BT, United Kingdom.
Restituito
Sophie
S
Brandon
Julia M
JM
Charles
Kelly J
KJ
Bawagan
Hinayana
H
Freeman
Katie B
KB
Pangalos
Menelas N
MN
Calver
Andrew R
AR
Moss
Stephen J
SJ
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D051381:Rats; D018080:Receptors, GABA-B / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D017783:Superior Cervical Ganglion / Q000166:cytology; D009435:Synaptic Transmission / Q000502:physiology
D048868:Adaptor Proteins, Signal Transducing; C484851:JAKMIP1 protein, human; C484853:Jakmip1 protein, rat; C484852:Marlin-1 protein, mouse; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D018080:Receptors, GABA-B