Glutamate transporters phosphorylation

Conradt, M. and Stoffel, W. (1997) Inhibition of the high-affinity brain glutamate transporter GLAST-1 via direct phosphorylation../. Neurochem. 68,1244-1251. 

Casado M., Bendahan A., ZafraF., DanboltN. C., Aragon C., Gimenez C., and Kanner B. I. (1993). Phosphorylation and modulation of brain glutamate transporters by protein kinase C. J. Biol. Chem. 268 27313-27317. 

Posttranslational regulation of glutamate transporters includes changes in cell surface expression due to trafficking between the plasma membrane and intracellular compartments, and modulation of transport activity by direct phosphorylation, redox modulation of sulfhydryl groups and inhibition by arachidonic acid and other ci5-polyunsaturated fatty acids. 

Direct phosphorylation of the glutamate transporter proteins themselves has only been reported for GLT and GLAST. Protein kinase C phosphorylates GLAST and thereby reduces the transport activity to 25% with no change in cell surface expression (Conradt and Stoffel, 1997). GLT was originally reported to be stimulated by phosphorylation of serine-113 (Casado et al., 1993), but a recent report (Tan et al., 1999) suggests that the protein kinase-C-mediated stimulation represents an effect of the expression system used rather than an effect on GLT. Further studies are required to sort out the controversy. 

Page G., Peeters M., Najimi M., Maloteaux J. M., and Hermans E. (2001). Modulation of the neuronal dopamine transporter activity by the metabotropic glutamate receptor mGluR5 in rat striatal synaptosomes through phosphorylation mediated processes. J. Neurochem. 76 1282-1290. 

Citrin is an aspartate-glutamate antiporter that has a role both in the urea cycle and in the malate aspartate shuttle. It is necessary for the transport of aspartate produced in the mitochondria into the cytosol, where it is used by AS. Its role in the malate-aspartate shuttle is to transport cytosolic NADH reducing equivalents into the mitochondria, where they are used in oxidative phosphorylation. Defects in citrin cause citrullinemia type II. Patients manifest later-onset intermittent hyperammonemic encephalopathy as in HHH syndrome. 

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