Receptor Desensitization, Internalization, and Recycling

Receptor activation and downstream signaling events are typically followed by receptor desensitization, the process by which the receptor becomes refractory to continued stimulation within seconds to minutes of agonist exposure. This is followed in turn by internalization, a process whereby the receptor is sequestered from the cell surface to intracellular 

Receptor desensitization is commonly caused by receptor internalization, whereby the receptor is removed from its location on the membrane into the cytoplasm, and then either degraded or recycled back to the surface by two main mechanisms. The level of cell-surface expression of a chemokine receptor is a balance between the rate of internalization and the rate of recovery, which can occur via de novo receptor production or receptor recycling, and which in some cases is a constitutive process (Pelchen-Matthews et al., 1999). Internalization is dramatically increased in the presence of agonist, and it is an active process, as internalization is almost entirely prevented at temperatures below 16°C (von Zastrow and Kobilka, 1994). There appear to be two main mechanisms of chemokine receptor internalization 1) the classical recruitment of arrestin to the receptor, resulting in the formation of a clathrin-coated vesicle around the receptor and subsequent internalization, and 2) internalization via clathrin-independent pathways. 

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