title: Dopamine receptor interacting proteins: targeting neuronal calcium sensor-1/D2 dopamine receptor interaction for antipsychotic drug development.
abstract: D2 dopamine receptors (D2Rs) represent an important class of receptors in the pharmacological development of novel therapeutic drugs for the treatment of schizophrenia. Recent research into D2R signaling suggests that receptor properties are dependent on interaction with a cohort of dopamine receptor interacting proteins (DRIPs) within a macromolecular structure termed the signalplex. One component of this signalplex is neuronal calcium sensor 1 (NCS-1) a protein found to regulate the phosphorylation, trafficking, and signaling profile of the D2R in neurons. It has also been found that NCS-1 can contribute to the pathology of schizophrenia and may play a role in the efficacy of antipsychotic drug medication in the brain. In this review we discuss how the selective targeting of a DRIP, such as NCS-1, can be utilized as a novel strategy of drug design for the creation of new therapeutics for a disease such as schizophrenia. Using a fluorescence polarization assay we explore how the ability to detect changes in D2R/NCS-1 interaction can be exploited as an effective screening tool in the isolation and development of lead compounds for antipsychotic drug development. This line of work explores a novel direction in targeting D2Rs via their signalplex components and supports the notion that receptor interacting proteins represent an emerging new class of molecular targets for pharmacological drug development.
authors.affiliation: Department of Molecular Neuroscience, Krasnow Institute for Advanced Study, George Mason University, 4400 University Drive, Fairfax, VA 22030, USA. nkabbani@gmu
authors.forename: Nadine
authors.initials: N
authors.lastname: Kabbani
authors.forename: Mathew P
authors.initials: MP
authors.lastname: Woll
authors.forename: Jacob C
authors.initials: JC
authors.lastname: Nordman
authors.forename: Robert
authors.initials: R
authors.lastname: Levenson
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D055808:Drug Discovery / Q000379:methods*; D018390:Gene Targeting / Q000379:methods*; D006801:Humans; D051580:Neuronal Calcium-Sensor Proteins / Q000378:metabolism*; D009479:Neuropeptides / Q000378:metabolism*; D010766:Phosphorylation / Q000235:genetics; D021381:Protein Transport / Q000235:genetics; D017448:Receptors, Dopamine D2 / Q000378:metabolism* / Q000502:physiology; D012559:Schizophrenia / Q000188:drug therapy / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics
chemical_list: D014150:Antipsychotic Agents; D051580:Neuronal Calcium-Sensor Proteins; D009479:Neuropeptides; D017448:Receptors, Dopamine D2; C101464:frequenin calcium sensor proteins