Glutamate Receptor Stimulation Up-Regulates Glutamate Uptake in Human Muller Glia Cells
Por:
Maria Lopez-Colome, Ana, Lopez, Edith, Mendez-Flores, Orquidia G., Ortega, Arturo
Publicada:
1 jul 2016
Resumen:
Glutamate, the main excitatory amino acid in the vertebrate retina, is a
well know activator of numerous signal transduction pathways, and has
been critically involved in long-term synaptic changes acting through
ionotropic and metabotropic glutamate receptors. However, recent
findings underlining the importance of intensity and duration of
glutamate stimuli for specific neuronal responses, including
excitotoxicity, suggest a crucial role for Na+-dependent glutamate
transporters, responsible for the removal of this neurotransmitter from
the synaptic cleft, in the regulation of glutamate-induced signaling.
Transporter proteins are expressed in neurons and glia cells, albeit
most of glutamate uptake occurs in the glial compartment. Within the
retina, Muller glia cells are in close proximity to glutamatergic
synapses and participate in the recycling of glutamate through the
glutamate/glutamine shuttle. In this context, we decided to investigate
a plausible role of glutamate as a regulatory signal for its own
transport in human retinal glia cells. To this end, we determined
[H-3]-D-aspartate uptake in cultures of spontaneously immortalized
human Muller cells (MIO-M1) exposed to distinct glutamatergic ligands. A
time and dose-dependent increase in the transporter activity was
detected. This effect was dependent on the activation of the N-methyl
D-aspartate subtype of glutamate receptors, due to a dual effect: an
increase in affinity and an augmented expression of the transporter at
the plasma membrane, as established via biotinylation experiments.
Furthermore, a NMDA-dependent association of glutamate transporters with
the cystoskeletal proteins ezrin and glial fibrillary acidic protein was
also found. These results add a novel mediator of the glutamate
transporter modulation and further strengthen the notion of the critical
involvement of glia cells in synaptic function.
Filiaciones:
Maria Lopez-Colome, Ana:
Univ Nacl Autonoma Mexico, Div Neurociencias, Inst Fisiol Celular, Mexico City 04510, DF, Mexico
Lopez, Edith:
Univ Nacl Autonoma Mexico, Div Neurociencias, Inst Fisiol Celular, Mexico City 04510, DF, Mexico
Mendez-Flores, Orquidia G.:
Inst Politecn Nacl, Ctr Invest & Estudios Avanzados, Dept Toxicol, Lab Neurotoxicol, Apartado Postal 14-740, Mexico City 07360, DF, Mexico
Ortega, Arturo:
Inst Politecn Nacl, Ctr Invest & Estudios Avanzados, Dept Toxicol, Lab Neurotoxicol, Apartado Postal 14-740, Mexico City 07360, DF, Mexico
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