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.
"The majority of the studies discussed in this section derive from interactomics approaches, with MAP1B interacting partners listed in Table 2. MAP1B interacts with several ligand-gated ion channels or transmembrane receptors and shows different physiological effects in each case. The q1 and q2 subunits of the ionotropic Cl 2 -permeable GABAcR interact with MAP1B HC, anchoring the channel subunits to microtubules, modifying channel activity and reducing its sensitivity (Hanley et al., 1999; Billups et al., 2000; Pattnaik et al., 2000). LC1 and LC2 bind to Stargazin (Ives et al., 2004), a protein involved in AMPAR trafficking toward the synapses (Chen et al., 2000), which suggests a role for MAP1B in the regulation of AMPAR. "
"In a more recent development, classical MAPs have been found to bind to a wide variety of proteins with diverse functions. For example, proteins of the MAP1 family bind to receptors and ion channels –, postsynaptic density (PSD) proteins PSD-93 and PSD-95 , , signaling molecules (EPAC, PDZrhoGEF, Tiam1, casein kinase 1d, RASSF1a , –) and proteins involved in intracellular traffic –. Thus, our findings presented here add to a growing body of evidence that classical MAPs can play a role in signal transduction not only by directly modulating microtubule function, but also through their interaction with a variety of signal transduction proteins. "
[Show abstract][Hide abstract] ABSTRACT: Microtubule-associated proteins of the MAP1 family (MAP1A, MAP1B, and MAP1S) share, among other features, a highly conserved COOH-terminal domain approximately 125 amino acids in length. We conducted a yeast 2-hybrid screen to search for proteins interacting with this domain and identified α1-syntrophin, a member of a multigene family of adapter proteins involved in signal transduction. We further demonstrate that the interaction between the conserved COOH-terminal 125-amino acid domain (which is located in the light chains of MAP1A, MAP1B, and MAP1S) and α1-syntrophin is direct and occurs through the pleckstrin homology domain 2 (PH2) and the postsynaptic density protein 95/disk large/zonula occludens-1 protein homology domain (PDZ) of α1-syntrophin. We confirmed the interaction of MAP1B and α1-syntrophin by co-localization of the two proteins in transfected cells and by co-immunoprecipitation experiments from mouse brain. In addition, we show that MAP1B and α1-syntrophin partially co-localize in Schwann cells of the murine sciatic nerve during postnatal development and in the adult. However, intracellular localization of α1-syntrophin and other Schwann cell proteins such as ezrin and dystrophin-related protein 2 (DRP2) and the localization of the axonal node of Ranvier-associated protein Caspr1/paranodin were not affected in MAP1B null mice. Our findings add to a growing body of evidence that classical MAPs are likely to be involved in signal transduction not only by directly modulating microtubule function, but also through their interaction with signal transduction proteins.
PLoS ONE 11/2012; 7(11):e49722. DOI:10.1371/journal.pone.0049722 · 3.23 Impact Factor
"Similar to glutamate receptors yeast-two-hybrid screens were used intensively to identify intracellular interaction partners of GABAAR subunits, but turned out to be more laborious than with glutamate receptors. The first proteins to be identified by this technique were proteins involved in the assembly (chaperones) and trafficking (like MAP-1B, PLIC, GABARAP) (Hanley et al., 1999; Wang et al., 1999; Bedford et al., 2001). Kinases and phosphatases were also among the first proteins to be shown to interact with GABAARs (Brandon et al., 2002, 2003). "
[Show abstract][Hide abstract] ABSTRACT: GABA(A) receptors are clustered at synaptic sites to achieve a high density of postsynaptic receptors opposite the input axonal terminals. This allows for an efficient propagation of GABA mediated signals, which mostly result in neuronal inhibition. A key organizer for inhibitory synaptic receptors is the 93 kDa protein gephyrin that forms oligomeric superstructures beneath the synaptic area. Gephyrin has long been known to be directly associated with glycine receptor β subunits that mediate synaptic inhibition in the spinal cord. Recently, synaptic GABA(A) receptors have also been shown to directly interact with gephyrin and interaction sites have been identified and mapped within the intracellular loops of the GABA(A) receptor α1, α2, and α3 subunits. Gephyrin-binding to GABA(A) receptors seems to be at least one order of magnitude weaker than to glycine receptors (GlyRs) and most probably is regulated by phosphorylation. Gephyrin not only has a structural function at synaptic sites, but also plays a crucial role in synaptic dynamics and is a platform for multiple protein-protein interactions, bringing receptors, cytoskeletal proteins and downstream signaling proteins into close spatial proximity.
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.