G-protein-coupled receptor (GPCR) dimerization is a rapidly developing area of research investigating molecular mechanisms involved in receptor activation. Traditionally, GPCR were thought to function as monomeric units. However, in recent years dimer/oligomer formation has been reported for dozens of different GPCRs using a variety of different techniques including immunoprecipitation, resonance energy transfer, and bimolecular fluorescence complementation (reviewed in Angers et al. 2002; Park et al. 2004; Kerppola 2008). Homo- and hetero-dimerization between different families of GPCR have been reported to regulate ligand binding, second messenger activation, and receptor trafficking (George et al. 2002). GPCR dimerization has been reported to involve the N-terminal domain, transmembrane domains, and the C-terminal domain of interacting receptors, and agonists have been reported to increase, decrease, or have no effect on GPCR dimerization (Javitch 2004; Milligan 2004). While these studies suggest that dimerization may be a common property among GPCRs, the specific mechanisms and functional consequences of dimerization may be vastly different from one GPCR family to another. In the case of g-aminobutyric acid B (GABAb) receptors, the functional significance of dimerization is very clear. Heterodimerization between GABAbR1 and GABAbR2 receptors is essential for trafficking and expression of functional receptors on the plasma membrane (Jones et al. 1998; Kaupmann et al. 1998; White et al. 1998). However, for the majority of GPCRs studied to date the functional significance of dimerization remains unknown.

Twelve different serotonin receptors belonging to the GPCR superfamily have been identified in humans (Hoyer et al. 2002). Immunoprecipitation and resonance energy transfer techniques have been used as supportive evidence for 5-HT1A,

Center for Neuropharmacology & Neuroscience and Department of Psychiatry, 47 New Scotland Ave., MC-136 Albany Medical College, Albany, NY 12208, USA e-mail: [email protected]

G. Di Giovanni et al. (eds.), 5-HT2C Receptors in the Pathophysiology of CNS Disease, The Receptors 22, DOI 10.1007/978-1-60761-941-3_7, © Springer Science+Business Media, LLC 2011

5-HT1B, 5-HT1d, 5-HT2C, and 5-HT4 receptor dimers (Xie et al. 1999; Salim et al. 2002; Herrick-Davis et al. 2004; Berthouze et al. 2007). This chapter focuses on the current literature related to 5-HT2C receptor dimerization. Specific topics to be addressed include the biochemical and biophysical properties of 5-HT2C homodim-ers, the homodimer biogenesis, the functional significance of homodimerization, the homodimer interface, and the heterodimerization with splice variants, isoforms, and other 5-HT receptor subtypes. Areas where there are gaps in our knowledge are identified and potential experiments to address these issues are discussed.

Defeat Drugs and Live Free

Defeat Drugs and Live Free

Being addicted to drugs is a complicated matter condition that's been specified as a disorder that evidences in the obsessional thinking about and utilization of drugs. It's a matter that might continue to get worse and become disastrous and deadly if left untreated.

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