GISP binding to TSG101 increases GABABreceptor stability by down-regulating ESCRT-mediated lysosomal degradation
| Autor: | Simon Jack Ogden, David Holman, Sriharsha Kantamneni, William Fraser, Atsushi Nishimune, Sônia A. L. Corrêa, Kevin A. Wilkinson, Jeremy M. Henley, Marco Feligioni |
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| Rok vydání: | 2008 |
| Předmět: |
A-kinase-anchoring protein
Protein subunit A Kinase Anchor Proteins Down-Regulation Nerve Tissue Proteins Endosomes macromolecular substances Biology Biochemistry Article ESCRT Cell Line Cellular and Molecular Neuroscience Animals Humans TSG101 Cells Cultured gamma-Aminobutyric Acid G protein-coupled receptor Neurons Endosomal Sorting Complexes Required for Transport Brain Membrane Proteins Receptors GABA-A Transmembrane protein Rats Transport protein Cell biology DNA-Binding Proteins Cytoskeletal Proteins Protein Transport Receptors GABA-B Membrane protein Mutation Lysosomes Protein Binding Transcription Factors |
| Zdroj: | Journal of Neurochemistry. 107:86-95 |
| ISSN: | 1471-4159 0022-3042 |
| Popis: | The neuron-specific G protein-coupled receptor interacting scaffold protein (GISP) is a multidomain, brain-specific protein derived from the A-kinase anchoring protein-9 gene. We originally isolated GISP as an interacting partner for the GABA(B) receptor subunit GABA(B1). Here, we show that the protein tumour susceptibility gene 101 (TSG101), an integral component of the endosomal sorting machinery that targets membrane proteins for lysosomal degradation, also interacts with GISP. TSG101 co-immunoprecipitates with GISP from adult rat brain, and using GST pull-downs, we identified that the eighth coiled-coiled region of GISP is critical for TSG101 association. Intriguingly, although there is no direct interaction between GISP and the GABA(B2) subunit, their co-expression in HEK293 cells increases levels of GABA(B2). GISP also inhibits TSG101-dependent GABA(B2) down-regulation in human embryonic kidney 293 cells whereas over-expression of a mutant GISP lacking the TSG101 binding domain has no effect on GABA(B2) degradation. These data suggest that GISP can function as a negative regulator of TSG101-dependent lysosomal degradation of transmembrane proteins in neurons to promote receptor stability. |
| Databáze: | OpenAIRE |
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