TY - JOUR T1 - A Regulated Interaction of Syntaxin 1A with the Antidepressant-Sensitive Norepinephrine Transporter Establishes Catecholamine Clearance Capacity JF - The Journal of Neuroscience JO - J. Neurosci. SP - 1697 LP - 1709 DO - 10.1523/JNEUROSCI.23-05-01697.2003 VL - 23 IS - 5 AU - Uhna Sung AU - Subramaniam Apparsundaram AU - Aurelio Galli AU - Kristopher M. Kahlig AU - Valentina Savchenko AU - Sally Schroeter AU - Michael W. Quick AU - Randy D. Blakely Y1 - 2003/03/01 UR - http://www.jneurosci.org/content/23/5/1697.abstract N2 - Norepinephrine (NE) transporters (NETs) terminate noradrenergic synaptic transmission and represent a major therapeutic target for antidepressant medications. NETs and related transporters are under intrinsic regulation by receptor and kinase-linked pathways, and clarification of these pathways may suggest candidates for the development of novel therapeutic approaches. Syntaxin 1A, a presynaptic soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) protein, interacts with NET and modulates NET intrinsic activity. NETs colocalize with and bind to syntaxin 1A in both native preparations and heterologous systems. Protein kinase C activation disrupts surface NET/syntaxin 1A interactions and downregulates NET activity in a syntaxin-dependent manner. Syntaxin 1A binds the NH2 terminal domain of NET, and a deletion of this domain both eliminates NET/syntaxin 1A associations and prevents phorbol ester-triggered NET downregulation. Whereas syntaxin 1A supports the surface trafficking of NET proteins, its direct interaction with NET limits transporter catalytic function. These two contradictory roles of syntaxin 1A on NET appear to be linked and reveal a dynamic cycle of interactions that allow for the coordinated control between NE release and reuptake. ER -