The protein MAP-1B links GABAC receptors to the cytoskeleton at retinal synapses

Abstract

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.

Suppression of Neuronal Hyperexcitability and Associated Delayed Neuronal Death by Adenoviral Expression of GABACReceptors

“…The punctate pattern of the membrane immunoreactivity could not be discerned, but because hippocampal neurons abundantly express the microtubule-associated protein-1B (MAP-1B) (data not shown), aggregation into receptor patches is expected (Hanley et al, 1999). The distinctive pharmacology of GABA C receptors (insensitive to bicuculline, sensitive to picrotoxin, selectively activated by CACA, and selectively inhibited by I4AA) allowed for a definitive confirmation of the presence of this receptor in Ad-1 -GFP-transduced hippocampal neurons.…”

Microtubule-associated Protein 1S, a Short and Ubiquitously Expressed Member of the Microtubule-associated Protein 1 Family

“…Total RNA (5 g) was reverse-transcribed using oligo(dT) [12][13][14][15][16][17][18] and Superscript II Reverse Transcriptase (Invitrogen) and subsequently amplified by PCR using primers 5Ј-ACGAAT-TCTGGTGGTGGGTGGCGAGTGTGG-3Ј and 5Ј-ACGAATTCAACAGT-GCCCAGTCCCCAAAGG-3Ј and Taq DNA polymerase (Invitrogen) according to the manufacturer's instructions. 5 l of the reaction were analyzed on agarose gels.…”

“…On the other hand, there is evidence that the function of MAP1B and perhaps MAP1A goes beyond regulation of the neuronal cytoskeleton. MAP1B interacts with and changes the ligand affinity of specific ␥-amino butyric acid receptor subunits (17,18). There is also evidence that a fraction of MAP1B is inserted in the axonal plasma membrane, with its extracellular domains binding to myelin-associated glycoprotein expressed on the surface of glial cells (19).…”

Microtubule‐associated protein 1B: Novel paraneoplastic biomarker

“…9 Nevertheless, for cases lacking CRMP5 IgG, it is noteworthy that the MAP1B antigen is expressed in the retina and that mice genetically lacking MAP1B have retinal dysfunction as a phenotypic manifestation. [10][11][12] Neurological manifestations noted in 5 MAP1B-IgG-seropositive patients (chorea, 3; dystonia, 1; dyskinesia, 1) were plausibly attritutable in 4 to coexisting autoimmunity to other SCLC onconeural antigens. 13 Three patients who were CRMP5 IgG positive had chorea; a fourth patient with coexisting amphiphysin IgG had dystonia.…”