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- W4281288563 abstract "Excitatory amino acid transporters (EAAT/SLC1) mediate Na+-dependent uptake of extracellular glutamate and are potential drug targets for neurological disorders. Conventional methods to assess glutamate transport in vitro are based on radiolabels, fluorescent dyes or electrophysiology, which potentially compromise the cell's physiology and are generally less suited for primary drug screens. Here, we describe a novel label-free method to assess human EAAT function in living cells, i.e., without the use of chemical modifications to the substrate or cellular environment. In adherent HEK293 cells overexpressing EAAT1, stimulation with glutamate or aspartate induced cell spreading, which was detected in real-time using an impedance-based biosensor. This change in cell morphology was prevented in the presence of the Na+/K+-ATPase inhibitor ouabain and EAAT inhibitors, which suggests the substrate-induced response was ion-dependent and transporter-specific. A mechanistic explanation for the phenotypic response was substantiated by actin cytoskeleton remodeling and changes in the intracellular levels of the osmolyte taurine, which suggests that the response involves cell swelling. In addition, substrate-induced cellular responses were observed for cells expressing other EAAT subtypes, as well as in a breast cancer cell line (MDA-MB-468) with endogenous EAAT1 expression. These findings allowed the development of a label-free high-throughput screening assay, which could be beneficial in early drug discovery for EAATs and holds potential for the study of other transport proteins that modulate cell shape." @default.
- W4281288563 created "2022-05-24" @default.
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- W4281288563 date "2022-05-23" @default.
- W4281288563 modified "2023-10-14" @default.
- W4281288563 title "Impedance-Based Phenotypic Readout of Transporter Function: A Case for Glutamate Transporters" @default.
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- W4281288563 cites W1601563281 @default.
- W4281288563 cites W1686065874 @default.
- W4281288563 cites W1820155366 @default.
- W4281288563 cites W1823895387 @default.
- W4281288563 cites W1947320848 @default.
- W4281288563 cites W1968042434 @default.
- W4281288563 cites W1968226779 @default.
- W4281288563 cites W1969713114 @default.
- W4281288563 cites W1970103114 @default.
- W4281288563 cites W1974887005 @default.
- W4281288563 cites W1977805229 @default.
- W4281288563 cites W1980816722 @default.
- W4281288563 cites W1988594055 @default.
- W4281288563 cites W1991001144 @default.
- W4281288563 cites W1991870376 @default.
- W4281288563 cites W2002831064 @default.
- W4281288563 cites W2003982930 @default.
- W4281288563 cites W2010307662 @default.
- W4281288563 cites W2010655741 @default.
- W4281288563 cites W2015426350 @default.
- W4281288563 cites W2019631026 @default.
- W4281288563 cites W2026137741 @default.
- W4281288563 cites W2028279469 @default.
- W4281288563 cites W2032745109 @default.
- W4281288563 cites W2039392894 @default.
- W4281288563 cites W2051250439 @default.
- W4281288563 cites W2052225210 @default.
- W4281288563 cites W2066650294 @default.
- W4281288563 cites W2072914334 @default.
- W4281288563 cites W2078576469 @default.
- W4281288563 cites W2084567278 @default.
- W4281288563 cites W2092358916 @default.
- W4281288563 cites W2094673798 @default.
- W4281288563 cites W2105832751 @default.
- W4281288563 cites W2110065044 @default.
- W4281288563 cites W2110095330 @default.
- W4281288563 cites W2119737459 @default.
- W4281288563 cites W2125588561 @default.
- W4281288563 cites W2138328666 @default.
- W4281288563 cites W2146105715 @default.
- W4281288563 cites W2148578075 @default.
- W4281288563 cites W2150076474 @default.
- W4281288563 cites W2155840517 @default.
- W4281288563 cites W2157853053 @default.
- W4281288563 cites W2158496253 @default.
- W4281288563 cites W2224021986 @default.
- W4281288563 cites W2330761586 @default.
- W4281288563 cites W2520197417 @default.
- W4281288563 cites W2536295903 @default.
- W4281288563 cites W2587834899 @default.
- W4281288563 cites W2741063349 @default.
- W4281288563 cites W2770222691 @default.
- W4281288563 cites W2811262331 @default.
- W4281288563 cites W2868208638 @default.
- W4281288563 cites W2889004960 @default.
- W4281288563 cites W2889090195 @default.
- W4281288563 cites W2918069149 @default.
- W4281288563 cites W2940538042 @default.
- W4281288563 cites W2944946842 @default.
- W4281288563 cites W2967594566 @default.
- W4281288563 cites W2975132204 @default.
- W4281288563 cites W2978761157 @default.
- W4281288563 cites W3009492389 @default.
- W4281288563 cites W3014901194 @default.
- W4281288563 cites W3020979674 @default.
- W4281288563 cites W3084420951 @default.
- W4281288563 cites W3121253596 @default.
- W4281288563 cites W3125833523 @default.
- W4281288563 cites W3134446085 @default.
- W4281288563 cites W3152645126 @default.
- W4281288563 cites W3157181964 @default.
- W4281288563 cites W3168853210 @default.
- W4281288563 cites W3179730861 @default.
- W4281288563 cites W3185745673 @default.
- W4281288563 cites W3194299440 @default.
- W4281288563 cites W4205592094 @default.
- W4281288563 cites W4210979710 @default.
- W4281288563 cites W4232534952 @default.
- W4281288563 doi "https://doi.org/10.3389/fphar.2022.872335" @default.
- W4281288563 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/35677430" @default.