Journal article
Transport rate of EAAT2 is regulated by amino acid located at the interface between the scaffolding and substrate transport domains
Neurochemistry international, v 139, 104792
Oct 2020
PMID: 32668264
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Excitatory Amino Acid Transporters (EAATs) are plasma membrane proteins responsible for maintenance of low extracellular concentrations of glutamate in the CNS. Dysfunction in their activity is implicated in various neurological disorders. Glutamate transport by EAATs occurs through the movement of the central transport domain relative to the scaffold domain in the EAAT membrane protein. Previous studies suggested that residues located within the interface of these two domains in EAAT2, the main subtype of glutamate transporter in the brain, are involved in regulating transport rates. We used mutagenesis, structure-function relationship, surface protein expression and electrophysiology studies, in transfected COS-7 cells and oocytes, to examine residue glycine at position 298, which is located within this interface. Mutation G298A results in increased transport rate without changes in surface expression, suggesting a more hydrophobic and larger alanine results in facilitated transport movement. The increased transport rate does not involve changes in sodium affinity. Electrophysiological currents show that G298A increase both transport and anion currents, suggesting faster transitions through the transport cycle. This work identifies a region critically involved in setting the glutamate transport rate.
•Dysregulation of glutamate transport is involved in many CNS disorders.•The interface between transport and scaffold domains is involved in transport rate regulation.•Mutation G298A in glutamate transporter EAAT2 increases transport rate.•Increased transport does not involve changes in surface expression or sodium affinity.•Increased transport rate and anion currents suggest faster transport cycle transitions.
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Details
- Title
- Transport rate of EAAT2 is regulated by amino acid located at the interface between the scaffolding and substrate transport domains
- Creators
- Michael Duffield - Drexel UniversityAvkash Patel - Drexel UniversityOle V. Mortensen - Drexel UniversityDora Schnur - Drexel UniversityAneysis D. Gonzalez-Suarez - Laboratory of Molecular and Cellular Neuroscience, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, 20892, USA.Delany Torres-Salazar - Laboratory of Molecular and Cellular Neuroscience, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, 20892, USA.Andréia C.K. Fontana - Drexel University
- Publication Details
- Neurochemistry international, v 139, 104792
- Publisher
- Elsevier
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology
- Web of Science ID
- WOS:000564511800007
- Scopus ID
- 2-s2.0-85088137493
- Other Identifier
- 991019168845604721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology
- Neurosciences