James G. Townsel , Ph.D.
Professor

Physiology

(615) 327-6847
Fax (Fax)
1005 Dr. D.B. Todd Boulevard
Nashville, TN  37208

jtownsel@mmc.edu

CV or Bio (PDF)

Studies in my laboratory center on trafficking of the cholinergic choline cotransporter (ChCoT) in Limulus polyphemus. The ChCoT is rate limiting in the synthesis of releasable acetylcholine and thus its regulation is critical to the physiology of cholinergic transmission. A major component of this regulation involves the acute redistribution of the ChCoT to the plasma membrane as a result of high frequency impulse activity. Our laboratory used the selective irreversible ligand, hemicholinium-3 mustard (HCM), in providing the first evidence for the constitutive cycling of the ChCoT into the plasma membrane. Upon cloning of the cDNA in Limulus, we reported the phylogenetic relationship of the ChCoT's to the sodium dependent glucose transporters. Recent studies derive from observed similarities between the ChCoT and the well-studied insulin responsive glucose transporter (GLUT4). As has been reported in studies with GLUT4, horseradish peroxidase conjugated transferring coupled with diaminobenzidine and H2O2 treatment resulted in the ablation of selected endosomal compartments in isolated Limulus brain hemi-slice preparation and thus the interruption of the constitutive cycling of the ChCoT. A recruitment paradigm involving exposure of ablated hemi-slices to depolarizing concentrations of elevated potassium in Chao's resulted in the restoration of transport in these slices. Thus, these studies point to the presence of an uncharacterized endosome essential to the regulated trafficking of the ChCoT. On-going studies are aimed at identifying the endosomal compartments involved in both the constitutive and regulated trafficking of the ChCoT with a special emphasis on the role of rab proteins in this trafficking.