title: Cytoplasmic domain of δ subunit is important for the extra-synaptic targeting of GABAA receptor subtypes.
abstract: GABA(A) receptors (GABA(A)Rs) are hetero-pentameric chloride channels and the primary sites for fast synaptic inhibition. We have expressed recombinant γ2 and δ subunits of GABA(A)Rs in cultured hippocampal neurons to analyze the membrane targeting of synaptic and extra-synaptic GABA(A)Rs, a phenomenon not well understood. Our data demonstrate that the synaptic targeting of γ2-containing GABA(A)Rs (γ2-GABA(A)Rs) does not depend on the cytoplasmic loop of γ2 subunit, in parallel with previous findings, showing that the synaptic localization of γ2-GABA(A)Rs requires the TM4 domain of γ2 rather than the large cytoplasmic loop. On the other hand, we showed here that the extrasynaptic targeting of the δ-containing GABA(A)Rs (δ-GABA(A)Rs) depends on the cytoplasmic loop of δ subunit via an active or a passive mechanism. We also show that the amino acid sequences of δ loop is highly conserved across the whole span of vertebrate evolution suggesting an active role of δ loop in extra-synaptic targeting of corresponding receptor subtypes.
authors.affiliation: Department of Clinical Neurobiology, University of Heidelberg, Im Neuenheimer Feld 364, 69120 Heidelberg, Germany , Department of Molecular Biology and Genetics, Faculty of Engineering and Natural Sciences, Üsküdar University, Altunizade Mah. Haluk Türksoy Sok. No: 14, PK 34662 Üsküdar/İstanbul, Turkey.
authors.forename: Ayla
authors.initials: A
authors.lastname: Arslan
authors.forename: Jakob
authors.initials: J
authors.lastname: von Engelhardt
authors.forename: William
authors.initials: W
authors.lastname: Wisden
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003593:Cytoplasm / Q000235:genetics / Q000378:metabolism*; D004622:Embryo, Mammalian; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology; D051379:Mice; D008958:Models, Molecular; D009474:Neurons / Q000166:cytology*; D017434:Protein Structure, Tertiary; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D021381:Protein Transport / Q000502:physiology; D011963:Receptors, GABA-A / Q000235:genetics / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism*; D014162:Transfection
chemical_list: D021122:Protein Subunits; D011963:Receptors, GABA-A; D049452:Green Fluorescent Proteins
keywords: GABAA receptors; delta subunit; extra-synaptic; gamma-2 subunit; synaptic