Research Highlights: In Brief...

Syntaxin 1a and Amphetamine Fun

F Binda, C Dipace, E Bowton, SD Robertson, BJ Lute, JU Fog, M Zhang, N Sen, RJ Colbran, ME Gnegy, U Gether, JA Javitch, K Erreger and A Galli (2008). Syntaxin 1A Interaction with the Dopamine Transporter Promotes Amphetamine-Induced Dopamine Efflux. Mol. Pharmacol. 74 (4): 1101-1108.

Amphetamine (AMPH) is a psychostimulant with rewarding properties as a drug of abuse.  AMPH works on the dopamine transporter (DAT) by causing dopamine efflux through the transporter.  In this study, the authors demonstrated that AMPH-induced activation of CaMKII causes syntaxin 1a, a protein critical in mediating vesicle fusion to the plasma membrane, to bind to the DAT N-terminus with greater affinity and increase AMPH-induced dopamine efflux.  These results offer insight into the mechanism by which AMPH works as a drug of abuse, and may suggest the target for treatment of AMPH-related drug addiction.

 

Increased SERT activity and Autism

HC Prasad, JA Steiner, JS Sutcliffe and RD Blakely (2009). Enhanced activity of human serotonin transporter variants associated with autism. Phil. Trans. R. Soc. B. 364: 163-173.

This study elaborates on findings of two previous studies (Prasad et al. 2005. PNAS USA. 102: 11545-11550; Sutcliffe et al. 2005. Am. J. Hum. Genet. 77: 265-279) showing highly significant linkage between the human serotonin transporter (hSERT) gene (SLC6A4) and autism spectrum disorders (ASD).  In this study, the authors demonstrated that three variants in hSERT result in a gain-of-function.  This increase in transporter activity may contribute to the developmentally atypical aspects of ASD, and may suggest the mechanism by which serotonin plays a role in autism.