Tethering toxins and peptide ligands for modulation of neuronal function

Tethering genetically encoded peptide toxins or ligands close to their point of activity at the cell plasma membrane provides a new approach to the study of cell networks and neuronal circuits, as it allows selective targeting of specific cell populations, enhances the working concentration of the ligand or blocker peptide, and permits the engineering of a large variety of t-peptides (e.g., including use of fluorescent markers, viral vectors and point mutation variants). This review describes the development of tethered toxins (t-toxins) and peptides derived from the identification of the cell surface nicotinic acetylcholine receptor (nAChR) modulator lynx1, the existence of related endogenous cell surface modulators of nAChR and AMPA receptors, and the application of the t-toxin and t-neuropeptide technology to the dissection of neuronal circuits in metazoans.

► Cell specific action of toxins and neuropeptides by tethering. ► Design principles of tethered peptide ligands. ► T-toxins and t-neuropeptides can be used in a wide variety of species. ► Targeted expression of t-toxins/t-peptides for dissection of CNS circuits.