Proteins That Interact with 5HT2C Receptor Intracellular Loops

5-HT2C receptors interact with b-arrestin (mainly b-arrestin-2) via the second intracellular loop (Marion et al. 2004; 2006). b-Arrestin binding is tightly dependent on receptor phosphorylation on C-terminal serine and threonine residues and on RNA editing of 5-HT2C receptors (Marion et al. 2004). The unedited 5-HT2C-INI receptor is capable of interacting with b-arrestin-2 in the absence of agonist, leading to constitutive receptor internalization and its accumulation within endocytic vesicles. Application of inverse agonists results in the redistribution of 5- HT2C-INI receptors to the plasma membrane of HEK-293 cells (Marion et al. 2004; Chanrion et al. 2008). At the same time, fully edited 5-HT2C-VGV receptors, which display the lowest level of constitutive activity, do not associate with b-arrestin-2 in the absence of an agonist and are located primarily at the cell surface. However, upon agonist treatment, the fully edited 5-HT2C-VGV receptor associates with b-arrestin-2 and undergoes rapid internalization.

5-HT2C receptors physically interact via their third intracellular loop with the tumor suppressor phosphatase and tensin homolog (PTEN), an enzyme exhibiting both lipid and protein phosphatase activities (Ji et al. 2006). Interaction between 5-HT2C receptors and PTEN prevents agonist-induced receptor phosphorylation at C-terminal serine residues located in the receptor PDZ motif. Association of 5-HT2C receptors with PTEN occurs in dopaminergic neurons of the ventral tegmental area innervating the accumbens nucleus, which are tonically inhibited by activated 5-HT2C receptors (Ji et al. 2006). Therefore, regulation of 5-HT2C receptors functional activity mediated by the interaction with PTEN may play a role in mediating the reinforcing role of drugs (Bockaert et al. 2006).

Defeat Drugs and Live Free

Defeat Drugs and Live Free

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