Within the heterologous systems, ?2C-AR is poorly transported towards the plasma membrane . In contrast, in the neuroendocrine cell lines the receptor is efficiently targeted for the plasma membrane, suggesting a cell specific ?2C-AR intracellular trafficking . Overall, ?2C-AR remains the least characterized ?2- AR subtype, as well as the mechanisms regulating the receptor intracellular trafficking aren’t completely understood. However, a role of ?2C-AR inside the pathology of Raynaud Phenomenon has been suggested. This illness is characterized by enhanced vasoconstriction in response to cold, emotional pressure or exposure Sunitinib to vibrations . The involvement of an unknown ?2-AR subtype was recommended by early publications of Flavahan and Freedman groups, according to the observation that the ?2-AR stimulation modulates the vasoconstriction at decreased temperature, whereas ?1-AR has no impact . Subsequently, sophisticated work from Flavahan?s group demonstrated that the vascular tone at low-temperature is specifically modulated by the ?2C-AR subtype, which can be silent at 37?C however it is functional at reduced temperatures In the course of the last decade, important progress was created in understanding the mechanisms controlling the intracellular protein visitors in the folding webpage represented by the endoplasmic reticulum to the functional destination .
It has been located that many newly synthesized Sorafenib proteins are transported along the biosynthetic pathway in an inefficient manner . As an example, inside the GPCR class, only 50% of the newly synthesized ?- opioid receptors are transported to the plasma membrane .
The fate on the newly synthesized GPCR results from the interactions with several specialized proteins, generically named molecular chaperones . These molecular chaperones are heterogeneous, with diverse subcellular localization and have numerous outcomes on the chaperoned protein, like enhancing the folding status and favoring the transport, or determining intracellular retention and proteasomal degradation. As a result, it’s not surprising that interfering together with the activity or expression of diverse molecular chaperones has been found to alter the rate of intracellular transport for numerous proteins. Likewise, downregulation on the cellular levels of AHSA1, a HSP90 co-chaperone, enhanced the cell surface of CFTR ?508 mutant . In contrast, inhibition of HSP90 activity decreased the maturation price of insulin receptor and nicotinic receptors . Currently few particular pharamacological agents are readily available to modulate the activity of molecular chaperones. This deficit is partly compensated by a variety of non-specific compounds, named pharmacological chaperones, which have been shown to stabilize the misfolded proteins and permit their progression within the biosynthetic pathway .