Abstract
The system N transporter SN1 (also known as SNAT3) is enriched on perisynaptic astroglial cell membranes. SN1 mediates electroneutral and bidirectional glutamine transport, and regulates the intracellular as well as the extracellular concentrations of glutamine. We hypothesize that SN1 participates in the glutamate/γ-aminobutyric acid (GABA)-glutamine cycle and regulates the amount of glutamine supplied to the neurons for replenishment of the neurotransmitter pools of glutamate and GABA. We also hypothesize that its activity on the plasma membrane is regulated by protein kinase C (PKC)-mediated phosphorylation and that SN1 activity has an impact on synaptic plasticity. This review discusses reports on the regulation of SN1 by PKC and presents a consolidated model for regulation and degradation of SN1 and the subsequent functional implications. As SN1 function is likely also regulated by PKC-mediated phosphorylation in peripheral organs, the same mechanisms may, thus, have impact on e.g., pH regulation in the kidney, urea formation in the liver, and insulin secretion in the pancreas.
Highlights
Synaptic transmission at a chemical synapse is essential to many neuronal functions such as cognition, learning, and memory
With the characterization of the members of the Slc38 family of amino acid transporters, showing that they may work in concert to shuttle glutamine from astroglial cells to neurons, the theory on a glutamate/glutamate/γ-aminobutyric acid (GABA)-glutamine cycle has been revitalized
Cells were metabolically labeled with 32P-orthophosphate, stimulated with phorbol 12-myristate 13-acetate (PMA) and following immunoprecipitation and 2D-phosphopeptide mapping, we demonstrated that protein kinase C (PKC)-dependent phosphorylation in living cells was abolished selectively when a single serine residue was mutated (S52A) in the N-terminal of rat SN1, implicating this as the primary phosphorylation site
Summary
Synaptic transmission at a chemical synapse is essential to many neuronal functions such as cognition, learning, and memory. We hypothesize that its activity on the plasma membrane is regulated by protein kinase C (PKC)-mediated phosphorylation and that SN1 activity has an impact on synaptic plasticity. With the characterization of the members of the Slc38 family of amino acid transporters, showing that they may work in concert to shuttle glutamine from astroglial cells to neurons, the theory on a glutamate/GABA-glutamine cycle has been revitalized.
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