Mtap2 is a constituent of the protein network that regulates twik-related K+ channel expression and trafficking.
Twik-related K+ (TREK) channels produce background currents that regulate cell excitability. In vivo, TREK-1 is involved in neuronal processes including neuroprotection against ischemia, general anesthesia, pain perception, and mood. Recently, we demonstrated that A-kinase anchoring protein AKAP150 binds to a major regulatory domain of TREK-1, promoting drastic changes in channel regulation by polyunsaturated fatty acids, pH, and stretch, and by G-protein-coupled receptors to neurotransmitters and hormones. Here, we show that the microtubule-associated protein Mtap2 is another constituent of native TREK channels in the brain. Mtap2 binding to TREK-1 and TREK-2 does not affect directly channel properties but enhances channel surface expression and current density. This effect relies on Mtap2 binding to microtubules. Mtap2 and AKAP150 interacting sites in TREK-1 are distinct and both proteins can dock simultaneously. Their effects on TREK-1 surface expression and activation are cumulative. In neurons, the three proteins are simultaneously detected in postsynaptic dense bodies. AKAP150 and Mtap2 put TREK channels at the center of a complex protein network that finely tunes channel trafficking, addressing, and regulation.
Sandoz
Guillaume
G
Institut de Pharmacologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique Unité Mixte de Recherche 6097, Institut Paul Hamel, 06560 Valbonne Sophia-Antipolis, France.
Tardy
Magalie P
MP
Thümmler
Susanne
S
Feliciangeli
Sylvain
S
Lazdunski
Michel
M
Lesage
Florian
F
D054758:A Kinase Anchor Proteins / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites; D001921:Brain / Q000378:metabolism; D019556:COS Cells; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D004285:Dogs; D005260:Female; D047468:Immunoprecipitation; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism; D009154:Mutation; D009865:Oocytes / Q000378:metabolism; D024683:Potassium Channels, Tandem Pore Domain / Q000378:metabolism*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D021381:Protein Transport / Q000502:physiology; D014018:Tissue Distribution; D014162:Transfection; D014981:Xenopus
D054758:A Kinase Anchor Proteins; C520665:Akap5 protein, mouse; D008869:Microtubule-Associated Proteins; C079240:Mtap2 protein, mouse; D024683:Potassium Channels, Tandem Pore Domain; D020033:Protein Isoforms