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GISP binding to TSG101 increases GABA receptor stability by down-regulating ESCRT-mediated lysosomal degradation.

GISP binding to TSG101 increases GABA receptor stability by down-regulating ESCRT-mediated lysosomal degradation. Research Abstract Details 

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  • GISP binding to TSG101 increases GABA receptor stability by down-regulating ESCRT-mediated lysosomal degradation. Abstract Text:

    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.

    GISP binding to TSG101 increases GABA receptor stability by down-regulating ESCRT-mediated lysosomal degradation. Publishing Authors By Initials

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    GISP binding to TSG101 increases GABA receptor stability by down-regulating ESCRT-mediated lysosomal degradation. Journal Published:

    PUBLICATION TYPE: Research Support, Non-U.S. Gov

    Journal: Journal of neurochemistry

    VOLUME: 107

    Page Numbers: 86-95

    Journal Abbreviation: J. Neurochem.

    ISSN: 1471-4159

    DAY: 17

    MONTH: 07

    YEAR: 2008

    GISP binding to TSG101 increases GABA receptor stability by down-regulating ESCRT-mediated lysosomal degradation. Information

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    LANGUAGE: eng

    NlmUniqueID: 2985190

    GISP binding to TSG101 increases GABA receptor stability by down-regulating ESCRT-mediated lysosomal degradation. Keywords Mesh Terms:

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    Grant and Affiliation Information for GISP binding to TSG101 increases GABA receptor stability by down-regulating ESCRT-mediated lysosomal degradation.

    AFFILIATION: Department of Anatomy, MRC Centre for Synaptic Plasticity, School of Medical Sciences, University of Bristol, Bristol, UK.

    Country: England

    England Research PublicationEngland Research Publication

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    MEDLINETA: J Neurochem

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