Project Summary

Paul A. Slesinger, Ph.D., (Independent Investigator 2006) of Salk Institute for Biological Sciences, notes that a defect in the brain dopaminergic system is implicated in schizophrenia but the molecular nature of this defect remains unclear. Development of novel antipsychotics with fewer side-effects is greatly needed. Dopamine receptors belong to the family of G protein-coupled receptors (GPCR), and stimulation of these receptors leads to the activation of G proteins which, in turn, act on downstream proteins such as the G-protein-gated potassium (GIRK) channel. These channels can alter dopamine regulation by changing neuronal membrane excitability. Recently, Dr. Slesinger has discovered a novel type of G protein/GIRK channel regulator, sorting nexin 27 (SNX27). He will now try to determine if inhibitory GIRK signaling in the brain is regulated by SNX27. This type of regulation would represent a novel pathway for modulating GIRK signaling efficacy as well as for regulating the activity of GPCRs in neurons. The results could lead to the discovery of new drug targets for controlling dopamine activity in the brain, and thus aid in the development of improved medications for schizophrenia.

Program Area: SCHIZOPHRENIA/PSYCHOTIC DISORDERS

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