期刊
NEUROPSYCHOPHARMACOLOGY
卷 39, 期 1, 页码 131-155出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/npp.2013.242
关键词
receptor-receptor interactions; G protein-coupled receptors; moonlighting; heterodimerization; neurotherapeutic targets; neuropsychiatric disorders
资金
- Swedish Research Council [04X-715]
- Torsten and Ragnar Soderberg Foundation
- Hjarnfonden
- Marianne and Marcus Wallenberg Foundation
- Swedish Royal Academy of Sciences
- Ministry of Science and Innovation [SAF2011-24779, CSD2008-00005]
- ICREA Academia from the Catalan Institution for Research and Advanced Studies
There is serious interest in understanding the dynamics of the receptor-receptor and receptor-protein interactions in space and time and their integration in GPCR heteroreceptor complexes of the CNS. Moonlighting proteins are special multifunctional proteins because they perform multiple autonomous, often unrelated, functions without partitioning into different protein domains. Moonlighting through receptor oligomerization can be operationally defined as an allosteric receptor-receptor interaction, which leads to novel functions of at least one receptor protomer. GPCR-mediated signaling is a more complicated process than previously described as every GPCR and GPCR heteroreceptor complex requires a set of G protein interacting proteins, which interacts with the receptor in an orchestrated spatio-temporal fashion. GPCR heteroreceptor complexes with allosteric receptor-receptor interactions operating through the receptor interface have become major integrative centers at the molecular level and their receptor protomers act as moonlighting proteins. The GPCR heteroreceptor complexes in the CNS have become exciting new targets for neurotherapeutics in Parkinson's disease, schizophrenia, drug addiction, and anxiety and depression opening a new field in neuropsychopharmacology.
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