FRAPs receptors

The majority of the 5-HT receptor subtypes am heptahelical G protein-coupled receptors (GPCRs) with the noted exception of 5-HT3 receptors, which form ligand-gated ion channels (6,7). Thus, GPCR-interacting proteins, either soluble or transmembrane, stood out as some of the best characterized FRAPs. Together, 5-HT receptors and their FRAPs constitute a structural and functional network of proteins known as the receptosome (8). 

For years, it was thought that the cytosolic carboxyl termini as well as various intracellular loops of the 5-HT receptors bind to FRAPs. Efforts from our lab to identify FRAPs utilized yeast two-hybrid screens see Fig. 1 for an overview), phage display see Fig. 2 for an overview), and direct biochemical approaches (8-13). These studies led to the discovery of many 5-HT2A receptorinteracting proteins, including caveolin-1 (Cav-1), arrestin-2 (Arr-2), arrestin-3 (Arr-3), microtubule-associated protein-1A (MAP-1A), and postsynaptic density protein-95 (PSD-95) see Table 1). 

Combining affinity chromatography, two-dimensional electrophoresis, and mass spectroscopy, Becamel and colleagues pioneered a global proteomic approach to 5-HT receptosomes (Chapter 7). These groundbreaking studies employed either the entire or partial carboxyl terminus of the 5-HT2 receptors as bait and heralded the discovery of multiple FRAPs (14,15). Since then, the proteomic strategy has been successfully applied to other 5-HT receptor subtypes (16,17). 

Summary of Known FRAPs and Their Associated 5-HT Receptors... 

The subcellular distribution of the 5-HT receptors likely contributes to their distinct functions. In polarized cells, several lines of evidence support the notion that receptor interaction with FRAPs targets and anchors 5-HT receptors to the appropriate subcellular compartments and modulates receptor internalization. We should also keep in mind that although most studies described in this section capture only a static image, we have only recently begun to appreciate the... 

FRAPs Target 5-HT Receptors to Distinct Subcellular Regions... 

A subset of FRAPs and 5-HT receptors share ultrastructural similarities, suggesting their close proximities in specialized subcellular regions. Confocal and electron microscopy demonstrated a concentration of 5-HT2C receptors in the microvilli bordering the apical surface of the epithelial cells in the choroids plexus where they colocalize with Veli-3 and MUPP1, both of which have been... 

Interaction with different FRAPs could couple 5-HT receptors to alternative signaling pathways. As an example, the 5-HT2A receptor is classically thought to... 

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