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GISP binding to TSG101 increases GABA B receptor stability by down‐regulating ESCRT‐mediated lysosomal degradation
Author(s) -
Kantamneni Sriharsha,
Holman David,
Wilkinson Kevin A.,
Corrêa Sônia A. L.,
Feligioni Marco,
Ogden Simon,
Fraser William,
Nishimune Atsushi,
Henley Jeremy M.
Publication year - 2008
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2008.05580.x
Subject(s) - tsg101 , escrt , hek 293 cells , microbiology and biotechnology , endosome , protein subunit , transmembrane protein , biology , mutant , vacuolar protein sorting , receptor , protein degradation , biochemistry , chemistry , gene , microrna , microvesicles
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.