Addictive psychostimulants such as cocaine and amphetamines bind to the dopamine transporter (DAT) and alter its ability to recycle dopamine (DA), resulting in adverse psychological and physiological effects. Several of these stimulants also bind the sigma 1 receptor (S1R), which modulates signal amplification of neurotransmitters, calcium and potassium through protein‐protein interactions at the plasma membrane. The S1R is expressed in dopaminergic neurons however; a physiological relationship between DAT and S1R has not been identified. Here we investigate physical interaction between DAT and S1R through co‐immunoprecipitation techniques in COS7 cells expressing the two proteins. Our data support that DAT and S1R are at least involved in a single protein complex as antibodies against DAT also purify S1R and vice versa.Grant Support: This work is supported by an NIH Grants DA026947 and NS071122 awarded to HK.

Zinc is an essential micronutrient which is required for the function of hundreds of cellular enzymes. In addition, zinc is the second most abundant transition metal found in biological systems (iron is most abundant). However, the concentration of free zinc is nano to picomolar since most zinc is bound to proteins. This makes investigating the mechanism of zinc transport across the plasma membrane a challenge. Our interest has been to elucidate the mechanism of zinc transport mediated by one member of the ZIP family of proteins. To this end, we have developed a radiometric uptake assay to study the mechanism of zinc transport. In addition, we have expressed and purified specific domains of the protein to examine the role of these domains in zinc coordination and transport. Thus, using a mixture of biochemical and biophysical techniques, we have begun to describe the mechanism of zinc transport to gain insight into the function of this protein.