In vivo regulation of an Aplysia glutamate transporter, ApGT1, during long-term memory formation.
Regulation of glutamate transporters often accompanies glutamatergic synaptic plasticity. We investigated the mechanisms responsible for the increase in glutamate uptake associated with increased glutamate release at the Aplysia sensorimotor synapse during long-term sensitization (LTS) and long-term facilitation. An increase in the V(max) of transport, produced by LTS training, suggested that the increased glutamate uptake was due to an increase in the number of transporters in the membrane. We cloned a high-affinity, Na(+)-dependent glutamate transporter, ApGT1, from Aplysia central nervous system that is highly enriched in pleural sensory neurons, and in pleural-pedal synaptosome and cell/glial fractions. ApGT1, expressed in Xenopus oocytes, demonstrated a similar pharmacological profile to glutamate uptake in Aplysia synaptosome and cell/glial fractions (strong inhibition by threo-beta-benzyloxyaspartate and weak inhibition by dihydrokainate) suggesting that ApGT1 may be the primary glutamate transporter in pleural-pedal ganglia. Levels of ApGT1 and glutamate uptake were increased in synaptosomes 24 h after induction of LTS by electrical stimulation or serotonin. Regulation of ApGT1 during LTS appears to occur post-transcriptionally and results in an increased number of transporters in synaptic membranes. These results suggest that an increase in levels of ApGT1 is responsible, at least in part, for the long-term increase in glutamate uptake associated with long-term memory.
Collado
Maria Sol
MS
Department of Biology and Biochemistry, University of Houston, Houston, TX 77204-5001, USA.
Lyons
Lisa C
LC
Levenson
Jonathan M
JM
Khabour
Omar
O
Pita-Almenar
Juan D
JD
Schrader
Laura
L
Eskin
Arnold
A
D000595:Amino Acid Sequence; D027322:Amino Acid Transport System X-AG / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D001048:Aplysia / Q000378:metabolism / Q000502:physiology*; D003001:Cloning, Molecular; D004558:Electric Stimulation; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism; D017774:Long-Term Potentiation; D008568:Memory / Q000502:physiology; D008969:Molecular Sequence Data; D009457:Neuroglia / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D009865:Oocytes / Q000378:metabolism; D009928:Organ Specificity; D012333:RNA, Messenger / Q000096:biosynthesis; D012701:Serotonin / Q000494:pharmacology; D013570:Synaptic Membranes / Q000378:metabolism; D013574:Synaptosomes / Q000378:metabolism; D014982:Xenopus laevis
D027322:Amino Acid Transport System X-AG; D012333:RNA, Messenger; D012701:Serotonin; D018698:Glutamic Acid