The protein MAP-1B links GABA(C) receptors to the cytoskeleton at retinal synapses.
The ionotropic type-A and type-C receptors for the neurotransmitter gamma-aminobutyric acid (GABA(A) and GABA(C) receptors) are the principal sites of fast synaptic inhibition in the central nervous system, but it is not known how these receptors are localized at GABA-dependent synapses. GABA(C) receptors, which are composed of rho-subunits, are expressed almost exclusively in the retina of adult vertebrates, where they are enriched on bipolar cell axon terminals. Here we show that the microtubule-associated protein 1B (MAP-1B) specifically interacts with the GABA(C) rho1 subunit but not with GABA(A) receptor subunits. Furthermore, GABA(C) receptors and MAP-1B co-localize at postsynaptic sites on bipolar cell axon terminals. Co-expression of MAP-1B and the rho1 subunit in COS cells results in a dramatic redistribution of the rho1 subunit. Our observations suggest a novel mechanism for localizing ionotropic GABA receptors to synaptic sites. This mechanism, which is specific for GABA(C) but not GABA(A) receptors, may allow these receptor subtypes, which have distinct physiological and pharmacological properties, to be differentially localized at inhibitory synapses.
Hanley
J G
JG
Department of Pharmacology, University College, London, UK.
Koulen
P
P
Bedford
F
F
Gordon-Weeks
P R
PR
Moss
S J
SJ
D000199:Actins / Q000502:physiology; D000818:Animals; D001692:Biological Transport; D019556:COS Cells; D002417:Cattle; D003599:Cytoskeleton / Q000502:physiology*; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000502:physiology*; D011485:Protein Binding; D051381:Rats; D018079:Receptors, GABA / Q000502:physiology*; D011963:Receptors, GABA-A / Q000502:physiology; D011993:Recombinant Fusion Proteins; D012160:Retina / Q000502:physiology*; D012441:Saccharomyces cerevisiae / Q000235:genetics; D013569:Synapses / Q000502:physiology*; D014404:Tubulin / Q000502:physiology
D000199:Actins; C087200:GABA-C receptor; D008869:Microtubule-Associated Proteins; D018079:Receptors, GABA; D011963:Receptors, GABA-A; D011993:Recombinant Fusion Proteins; D014404:Tubulin; C085284:microtubule-associated protein 1B