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GISP: a novel brain‐specific protein that promotes surface expression and function of GABA B receptors
Author(s) -
Kantamneni Sriharsha,
Corrêa Sônia A. L.,
Hodgkinson Gina K.,
Meyer Guido,
Vinh Ngoc Nga,
Henley Jeremy M.,
Nishimune Atsushi
Publication year - 2007
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.1471-4159.2006.04271.x
Subject(s) - postsynaptic density , microbiology and biotechnology , gabab receptor , postsynaptic potential , protein subunit , neurotransmission , receptor , g protein coupled inwardly rectifying potassium channel , baclofen , biology , g protein coupled receptor , hippocampal formation , gabaa receptor , chemistry , signal transduction , neuroscience , g protein , biochemistry , agonist , gene
Synaptic transmission depends on the regulated surface expression of neurotransmitter receptors, but many of the cellular processes required to achieve this remain poorly understood. To better define specific mechanisms for the GABA B receptor (GABA B R) trafficking, we screened for proteins that bind to the carboxy‐terminus of the GABA B1 subunit. We report the identification and characterization of a novel 130‐kDa protein, GPCR interacting scaffolding protein (GISP), that interacts directly with the GABA B1 subunit via a coiled‐coil domain. GISP co‐fractionates with GABA B R and with the postsynaptic density and co‐immunoprecipitates with GABA B1 and GABA B2 from rat brain. In cultured hippocampal neurons, GISP displays a punctate dendritic distribution and has an overlapping localization with GABA B Rs. When co‐expressed with GABA B Rs in human embryonic kidney cells, GISP promotes GABA B R surface expression and enhances both baclofen‐evoked extracellular signal‐regulated kinase (ERK) phosphorylation and G‐protein inwardly rectifying potassium channel (GIRK) currents. These results suggest that GISP is involved in the forward trafficking and stabilization of functional GABA B Rs.