Journal Article

Caveolin-1 Sensitivity of Excitatory Amino Acid Transporters EAAT1, EAAT2, EAAT3, and EAAT4

Elvira, Bernat, Abousaab, Abeer, Lang, Florian, Warsi, Jamshed

2016

Overview

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.

• Publisher: Springer US,Springer Nature B.V
• Subject: Amino acids / Animals / Biochemistry / Biological Transport / Biomedical and Life Sciences / Caveolin 1 - genetics / Caveolin 1 - metabolism / Cellular biology / Excitatory Amino Acid Transporter 1 - genetics / Excitatory Amino Acid Transporter 1 - metabolism / Excitatory Amino Acid Transporter 2 - genetics / Excitatory Amino Acid Transporter 2 - metabolism / Excitatory Amino Acid Transporter 3 - genetics / Excitatory Amino Acid Transporter 3 - metabolism / Excitatory Amino Acid Transporter 4 - genetics / Excitatory Amino Acid Transporter 4 - metabolism / Gene Expression / Glutamic Acid - metabolism / Human Physiology / Humans / Life Sciences / Membranes / Neurons / Oocytes - metabolism / Proteins / Xenopus laevis