GISP: a novel brain-specific protein that promotes surface expression and function of GABA(B) receptors.
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.
Kantamneni
Sriharsha
S
MRC Centre for Synaptic Plasticity, Department of Anatomy, School of Medical Sciences, University of Bristol, Bristol, UK.
Corrêa
Sônia A L
SA
Hodgkinson
Gina K
GK
Meyer
Guido
G
Vinh
Ngoc Nga
NN
Henley
Jeremy M
JM
Nishimune
Atsushi
A
D054758:A Kinase Anchor Proteins; D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D019921:Biotinylation / Q000379:methods; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000502:physiology*; D004622:Embryo, Mammalian; D018755:GABA Agonists / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000502:physiology; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D047468:Immunoprecipitation / Q000379:methods; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008970:Molecular Weight; D016296:Mutagenesis / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D017434:Protein Structure, Tertiary / Q000502:physiology; D021381:Protein Transport / Q000187:drug effects / Q000502:physiology; D051381:Rats; D018080:Receptors, GABA-B / Q000737:chemistry / Q000502:physiology*; D013347:Subcellular Fractions / Q000187:drug effects / Q000502:physiology; D014162:Transfection; D020798:Two-Hybrid System Techniques
D054758:A Kinase Anchor Proteins; C486537:Akap9 protein, rat; D003598:Cytoskeletal Proteins; D018755:GABA Agonists; D009419:Nerve Tissue Proteins; D018080:Receptors, GABA-B; D001418:Baclofen