title: Caveolin-1 Sensitivity of Excitatory Amino Acid Transporters EAAT1, EAAT2, EAAT3, and EAAT4.
abstract: Excitatory amino acid transporters EAAT1 (SLC1A3), EAAT2 (SLC1A2), EAAT3 (SLC1A1), and EAAT4 (SLC1A6) serve to clear L-glutamate from the synaptic cleft and are thus important for the limitation of neuronal excitation. EAAT3 has previously been shown to form complexes with caveolin-1, a major component of caveolae, which participate in the regulation of transport proteins. The present study explored the impact of caveolin-1 on electrogenic transport by excitatory amino acid transporter isoforms EAAT1-4. To this end cRNA encoding EAAT1, EAAT2, EAAT3, or EAAT4 was injected into Xenopus oocytes without or with additional injection of cRNA encoding caveolin-1. The L-glutamate (2 mM)-induced inward current (I Glu) was taken as a measure of glutamate transport. As a result, I Glu was observed in EAAT1-, EAAT2-, EAAT3-, or EAAT4-expressing oocytes but not in water-injected oocytes, and was significantly decreased by coexpression of caveolin-1. Caveolin-1 decreased significantly the maximal transport rate. Treatment of EAATs-expressing oocytes with brefeldin A (5 µM) was followed by a decrease in conductance, which was similar in oocytes expressing EAAT together with caveolin-1 as in oocytes expressing EAAT1-4 alone. Thus, caveolin-1 apparently does not accelerate transporter protein retrieval from the cell membrane. In conclusion, caveolin-1 is a powerful negative regulator of the excitatory glutamate transporters EAAT1, EAAT2, EAAT3, and EAAT4.
authors.affiliation: Department of Physiology I, University of Tübingen, Gmelinstr. 5, 72076, Tübingen, Germany.
authors.forename: Abeer
authors.initials: A
authors.lastname: Abousaab
authors.affiliation: Department of Physiology I, University of Tübingen, Gmelinstr. 5, 72076, Tübingen, Germany.
authors.forename: Jamshed
authors.initials: J
authors.lastname: Warsi
authors.affiliation: Department of Physiology I, University of Tübingen, Gmelinstr. 5, 72076, Tübingen, Germany.
authors.forename: Bernat
authors.initials: B
authors.lastname: Elvira
authors.affiliation: Department of Physiology I, University of Tübingen, Gmelinstr. 5, 72076, Tübingen, Germany. florian.lang@uni-tuebingen.de.
authors.forename: Florian
authors.initials: F
authors.lastname: Lang
mesh_terms: D000818:Animals; D001692:Biological Transport; D051242:Caveolin 1 / Q000235:genetics / Q000378:metabolism*; D027341:Excitatory Amino Acid Transporter 1 / Q000235:genetics / Q000378:metabolism*; D027342:Excitatory Amino Acid Transporter 2 / Q000235:genetics / Q000378:metabolism*; D050580:Excitatory Amino Acid Transporter 3 / Q000235:genetics / Q000378:metabolism*; D050581:Excitatory Amino Acid Transporter 4 / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D009865:Oocytes / Q000378:metabolism; D014982:Xenopus laevis
chemical_list: D051242:Caveolin 1; D027341:Excitatory Amino Acid Transporter 1; D027342:Excitatory Amino Acid Transporter 2; D050580:Excitatory Amino Acid Transporter 3; D050581:Excitatory Amino Acid Transporter 4; D018698:Glutamic Acid
keywords: GLAST; Glt-1; SLC1A1; SLC1A2; SLC1A3; SLC1A6