The Sushi domains of GABAB receptors function as axonal targeting signals
| Autor: | Barbara Biermann, Amyaouch Bradaia, Martin Gassmann, Klara Ivankova-Susankova, Markus Missler, Josef P. Kapfhammer, Valerie Besseyrias, Bernhard Bettler, Said Abdel Aziz |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Gene isoform
Signal peptide Patch-Clamp Techniques Protein subunit CD8 Antigens Recombinant Fusion Proteins GABAB receptor Biology Axonal Transport Hippocampus Synaptic Transmission Protein–protein interaction 03 medical and health sciences Glutamatergic Mice 0302 clinical medicine Protein structure Receptors GABA Animals Receptor Cells Cultured 030304 developmental biology Mice Knockout 0303 health sciences Mice Inbred BALB C General Neuroscience Cell Polarity Neural Inhibition Dendrites Articles Receptors GABA-A Axons Protein Structure Tertiary Protein Subunits Protein Transport nervous system Receptors GABA-B Mutation Neuroscience 030217 neurology & neurosurgery Signal Transduction |
| Zdroj: | Journal of Neuroscience; Vol 30 |
| ISSN: | 1529-2401 |
| Popis: | GABABreceptors are the G-protein-coupled receptors for GABA, the main inhibitory neurotransmitter in the brain. Two receptor subtypes, GABAB(1a,2)and GABAB(1b,2), are formed by the assembly of GABAB1aand GABAB1bsubunits with GABAB2subunits. The GABAB1bsubunit is a shorter isoform of the GABAB1asubunit lacking two N-terminal protein interaction motifs, the sushi domains. Selectively GABAB1aprotein traffics into the axons of glutamatergic neurons, whereas both the GABAB1aand GABAB1bproteins traffic into the dendrites. The mechanism(s) and targeting signal(s) responsible for the selective trafficking of GABAB1aprotein into axons are unknown. Here, we provide evidence that the sushi domains are axonal targeting signals that redirect GABAB1aprotein from its default dendritic localization to axons. Specifically, we show that mutations in the sushi domains preventing protein interactions preclude axonal localization of GABAB1a. When fused to CD8α, the sushi domains polarize this uniformly distributed protein to axons. Likewise, when fused to mGluR1a the sushi domains redirect this somatodendritic protein to axons, showing that the sushi domains can override dendritic targeting information in a heterologous protein. Cell surface expression of the sushi domains is not required for axonal localization of GABAB1a. Altogether, our findings are consistent with the sushi domains functioning as axonal targeting signals by interacting with axonally bound proteins along intracellular sorting pathways. Our data provide a mechanistic explanation for the selective trafficking of GABAB(1a,2)receptors into axons while at the same time identifying a well defined axonal delivery module that can be used as an experimental tool. |
| Databáze: | OpenAIRE |
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