NonPDZ Proteins That Interact with 5HT2C Receptors C Terminus

5-HT2C receptors also interact with non-PDZ proteins. These include CaM, which binds to the 5-HT2C receptor C-terminus (Becamel et al. 2002). An additional putative CaM binding motif has been identified in the second intracellular loop of the 5-HT2C receptor (Turner and Raymond 2005). Labasque et al. have demonstrated that CaM binds to a prototypic Ca2+-dependent "1-10" CaM-binding motif located in the proximal region of the 5-HT2C receptor C-terminus in an agonist-dependent manner (Labasque et al. 2008). Mutation of this motif inhibited both b-arrestin recruitment by the 5-HT2C receptor and 5-HT-induced ERK1/2 activation in HEK 293 cells. Therefore, CaM bound to the juxtamembrane region of the 5-HT2C receptor C-terminus might function to stabilize 5-HT2C receptor-b-arrestin interaction (Labasque et al. 2008).

Proteomic screens also have demonstrated interactions of the 5-HT2C receptor C-terminal domain with proteins of the cytoskeleton (b-actin, spectrin aII chain, a and b chains of CAPZ) and with two other proteins with unknown functions -PTD4, a putative GTP-binding protein and PICOT (PKC 9-interacting protein), which contains a thioredoxin homology domain that is involved in the regulation of the thioredoxin system (Becamel et al. 2002).

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