GABA receptor rho1 subunit interacts with a novel splice variant of the glycine transporter, GLYT-1.
Ionotropic gamma-aminobutyric acid (GABA(A) and GABA(C)) receptors mediate fast synaptic inhibition in the central nervous system. GABA(C) receptors are expressed predominantly in the retina on bipolar cell axon terminals, and are thought to mediate feedback inhibition from GABAergic amacrine cells. Utilizing the yeast two-hybrid system, we previously identified MAP1B as a binding partner of the GABA(C) receptor rho1 subunit. Here we describe the isolation of an additional rho1 interacting protein: a novel C-terminal variant of the glycine transporter GLYT-1. We show that GLYT-1 exists as four alternatively spliced mRNAs which encode proteins expressing one of two possible intracellullar N- and C-terminal domains. Variants containing the novel C terminus efficiently transport glycine when expressed in COS cells, but with unusual kinetics. We have confirmed the interaction between the novel C terminus and rho1 subunit and demonstrated binding in heterologous cells. This interaction may be crucial for the integration of GABAergic and glycinergic neurotransmission in the retina.
Hanley
J G
JG
Laboratory for Molecular Cell Biology and Department of Pharmacology, University College London, Gower St., London, WC1E 6BT, United Kingdom.
Jones
E M
EM
Moss
S J
SJ
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D026921:Amino Acid Transport Systems, Neutral; D000818:Animals; D001483:Base Sequence; D019556:COS Cells; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D002417:Cattle; D003001:Cloning, Molecular; D017931:DNA Primers; D015723:Gene Library; D014644:Genetic Variation; D005998:Glycine / Q000378:metabolism*; D050487:Glycine Plasma Membrane Transport Proteins; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics; D018079:Receptors, GABA / Q000737:chemistry / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D012160:Retina / Q000378:metabolism*; D012441:Saccharomyces cerevisiae; D016415:Sequence Alignment; D012964:Sodium / Q000378:metabolism; D014162:Transfection
D026921:Amino Acid Transport Systems, Neutral; D002352:Carrier Proteins; D017931:DNA Primers; C087200:GABA-C receptor; D050487:Glycine Plasma Membrane Transport Proteins; D012333:RNA, Messenger; D018079:Receptors, GABA; D011994:Recombinant Proteins; D012964:Sodium; D005998:Glycine