The neurosteroid allopregnanolone upregulates glutamate transport in Schwann cells by changing the surface density of the EAAC1/EAAT3 glutamate transporter

Glutamate has been recently involved in the proliferation and differentiation of Schwann cells, the myelinating cells of the Peripheral Nervous System. Thus, the control of extracellular glutamate level may be crucial for Schwann cell physiology. We recently observed that functional glutamate transporters were expressed by Schwann cells and modulated by exposure to 10 nM allopregnanolone (ALLO), a progesterone's metabolite. Aim of this study was to identify the molecular mechanisms by which ALLO modulated glutamate uptake. We found that transport up-regulation did not involve protein neo-synthesis and was prevented by actin depolimerization, suggesting a change in the transporters' trafficking. To verify this hypothesis, Schwann cells were transfected with the GFP-tagged EAAC1 transporter and its surface density was measured by Total Internal Reflection Microscopy (TIRFM). ALLO induced the actin cytoskeleton reorganization and caused the EAAC1 redistribution from intracellular compartments to the plasma membrane, at the tips of filopodia structures. Taken together, these data demonstrate that ALLO up-regulates glutamate transport by increasing the delivery of EAAC1 to the cell surface.