|
Mechanisms of Receptor and Transporter Trafficking
Dopamine Transporter: Are Psychostimulants in Your Neighborhood Forcing You To Move?
Aurelio Galli, Ph.D., Vanderbilt University School of Medicine
Dr. Aurelio Galli presented research in which his team attempted to characterize amphetamine-induced loss of transporter capacity over time. The results showed a temporal correlation between the loss of transporter activity and hDAT cell surface expression. Data suggest strongly that the amphetamine (AMPH) reaction of hDAT transport capacity results from the removal of active carriers in the plasma membrane. Further research implicates DAT trafficking in the hormonal regulation of dopaminergic signaling and shows that insulin is a tool for regulating the AMPH-induced loss of DAT activity and cell surface expression.
|
AMPA Receptor Assembly Determined by Q/R Editing
Ingo Greger, Ph.D., Medical Research Council Laboratory of Molecular Biology
Dr. Ingo Greger and his team identified an internal GluR2 pool within the endoplasmic reticulum (ER). Reversion to the exonically encoded Gln resulted in rapid release from the ER and increased surface expression of GluR2. This research leads to the conclusion that Arg607 acts as a master switch, controlling ER-exit. Also, Arg607 may ensure the availability of GluR2 for incorporation into AMPARs. Such a mechanism could explain the presence of GluR2 in the majority of AMPARs in the brain. Greger presented a model in which Arg607 controls receptor trafficking by regulating the assembly of subunit dimmer intermediates into tetrameric channels that are competent for ER export.
|
Signaling Mechanisms for Synaptic Plasticity
J. Julius Zhu, Ph.D., University of Virginia School of Medicine
Dr. Julius Zhu described efforts to better understand the signaling that controls AMPA receptor trafficking. His team examined the role of the small GTPases—Ras and Rap—in postsynaptic signaling during synaptic plasticity. Their work showed that Ras relays the NMDA-R and CaMKII signaling that drives the synaptic delivery of AMPA-Rs, with long cytoplasmic tails during long-term potentiation. In contrast, Rap mediates NMDA-R-dependent removal of synaptic AMPA-Rs, with only short cytoplasmic tails that occur during long-term depression. Understanding the signaling pathways that regulate AMPA-R trafficking can help scientists locate potential molecular targets for novel genetic and pharmacological therapies aimed at treating diseases that cause cognitive impairment.
|
|
|
Frontiers in Addiction Research
|
|