Protein kinase C-dependent remodeling of glutamate transporter function.
Glutamate is the predominant excitatory neurotransmitter in the mammalian central nervous system and is critical for essentially all physiological processes ranging from control of motor and somatosensory function to information processing and storage. Like many other small molecule neurotransmitters, transporters localized to the plasma membrane control the extracellular concentrations of glutamate. These transporters are both acutely and chronically regulated by several different mechanisms that presumably contribute to the protection of the nervous system from hypo- or hyper-glutamatergic function. In this review, we will describe our emerging understanding of one aspect of glutamate transporter regulation that is dependent on protein kinase C. More than a decade of extensive research on glutamate receptor-specific therapeutics has been driven by the hypothesis that these agents might be useful for pain management, treatment of schizophrenia or other psychiatric disorders, and prevention of neurodegenerative diseases. We assume that, in this modern era of drug discovery, understanding the endogenous regulatory mechanisms that are activated under physiological and pathological conditions will be required before one can target transporters for a ubiquitous neurotransmitter like glutamate.
Department of Pediatrics, Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA 19104-4318, USA.
Marco I
MI
González
Michael B
MB
Robinson
D027322:Amino Acid Transport System X-AG / Q000378:metabolism*; D000818:Animals; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000378:metabolism; D027342:Excitatory Amino Acid Transporter 2 / Q000378:metabolism; D050580:Excitatory Amino Acid Transporter 3 / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism; D020033:Protein Isoforms / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism
D027322:Amino Acid Transport System X-AG; D004791:Enzyme Inhibitors; D027342:Excitatory Amino Acid Transporter 2; D050580:Excitatory Amino Acid Transporter 3; D020033:Protein Isoforms; D018698:Glutamic Acid; D011493:Protein Kinase C