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GISP binding to TSG101 increases GABA receptor stability by down-regulating ESCRT-mediated lysosomal degradation.
- Source :
-
Journal of neurochemistry [J Neurochem] 2008 Oct; Vol. 107 (1), pp. 86-95. Date of Electronic Publication: 2008 Jul 17. - Publication Year :
- 2008
-
Abstract
- 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.
- Subjects :
- A Kinase Anchor Proteins
Animals
Cell Line
Cells, Cultured
Cytoskeletal Proteins
Down-Regulation physiology
Endosomal Sorting Complexes Required for Transport
Endosomes metabolism
Humans
Membrane Proteins metabolism
Mutation genetics
Nerve Tissue Proteins genetics
Protein Binding physiology
Protein Transport physiology
Rats
gamma-Aminobutyric Acid metabolism
Brain metabolism
DNA-Binding Proteins metabolism
Lysosomes metabolism
Nerve Tissue Proteins metabolism
Neurons metabolism
Receptors, GABA-A metabolism
Receptors, GABA-B metabolism
Transcription Factors metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1471-4159
- Volume :
- 107
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Journal of neurochemistry
- Publication Type :
- Academic Journal
- Accession number :
- 18643869
- Full Text :
- https://doi.org/10.1111/j.1471-4159.2008.05580.x