title: GLAST/EAAT1-induced glutamine release via SNAT3 in Bergmann glial cells: evidence of a functional and physical coupling.
abstract: Glutamate, the major excitatory transmitter in the vertebrate brain, is removed from the synaptic cleft by a family of sodium-dependent glutamate transporters profusely expressed in glial cells. Once internalized, it is metabolized by glutamine synthetase to glutamine and released to the synaptic space through sodium-dependent neutral amino acid carriers of the N System (SNAT3/slc38a3/SN1, SNAT5/slc38a5/SN2). Glutamine is then taken up by neurons completing the so-called glutamate/glutamine shuttle. Despite of the fact that this coupling was described decades ago, it is only recently that the biochemical framework of this shuttle has begun to be elucidated. Using the established model of cultured cerebellar Bergmann glia cells, we sought to characterize the functional and physical coupling of glutamate uptake and glutamine release. A time-dependent Na⁺-dependent glutamate/aspartate transporter/EAAT1-induced System N-mediated glutamine release could be demonstrated. Furthermore, D-aspartate, a specific glutamate transporter ligand, was capable of enhancing the co-immunoprecipitation of Na⁺-dependent glutamate/aspartate transporter and Na⁺-dependent neutral amino acid transporter 3, whereas glutamine tended to reduce this association. Our results suggest that glial cells surrounding glutamatergic synapses may act as sensors of neuron-derived glutamate through their contribution to the neurotransmitter turnover.
authors: Departamento de Genética y Biología Molecular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, México D.F, México.
authors: Zila
authors: Z
authors: Martínez-Lozada
authors: Alain M
authors: AM
authors: Guillem
authors: Marco
authors: M
authors: Flores-Méndez
authors: Luisa C
authors: LC
authors: Hernández-Kelly
authors: Carmelita
authors: C
authors: Vela
authors: Enrique
authors: E
authors: Meza
authors: Rossana C
authors: RC
authors: Zepeda
authors: Mario
authors: M
authors: Caba
authors: Angelina
authors: A
authors: Rodríguez
authors: Arturo
authors: A
authors: Ortega
mesh_terms: D026921:Amino Acid Transport Systems, Neutral / Q000378:metabolism*; D000818:Animals; D002450:Cell Communication / Q000502:physiology; D002642:Chick Embryo; D002645:Chickens; D027341:Excitatory Amino Acid Transporter 1 / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism* / Q000493:pharmacokinetics; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D061251:Primary Cell Culture; D011485:Protein Binding / Q000502:physiology; D012964:Sodium / Q000378:metabolism; D013569:Synapses / Q000378:metabolism; D014316:Tritium
chemical_list: D026921:Amino Acid Transport Systems, Neutral; D027341:Excitatory Amino Acid Transporter 1; C403222:system N protein 1; D005973:Glutamine; D014316:Tritium; D018698:Glutamic Acid; D012964:Sodium