Receptors recycling

Monensin Monensin (25 [xM, 30 minutes) elevates the pH in acidic compartments and inhibits receptor recycling by trapping receptors in endosomes (37). 

Figure 8 Ubiquitin and endocytosis. Receptors on the plasma membrane undergo monoubiquitination as a result of ligand (e.g., neurotransmitter). Ubiquitinated receptors bind to proteins called epsins, which in turn interact with adaptor proteins (adaptin) bound to clathrin-coated pits. Ubiquitination also functions to sort the internalized membrane protein into early endosomes, which directs them to degradation by lysosome through the multivesicular body. If ubiquitin from the endocytosed receptors is removed by an UBP, the receptor recycles back to the membrane. Proteasome inhibitors block endocytotic degradation of some proteins such as glutamate receptor subunits indicating a possible role for the proteasome.

Ferro-heme + [HPX-Receptor] -> Recycle to surface + MHBP 4 (intraceUular transport)... 

Finally, continuous exposure of certain receptors to their macromolecular ligands can lead to rapid downregulation of cell surface receptors, especially if receptor recycling within the cells is incomplete. Fortunately, expression of many receptors, for example for certain cytokines, growth hormones and adhesion factors, can be extensively upregulated in the disease process and this can result in disease-induced drug-targeting. 

Chauvin, S., M. Bencsik,T. Bambino, and R.A. Nissenson. 2002. Parathyroid hormone receptor recycling role of receptor dephosphorylation and beta-arrestin. Mol. Endocrinol. 16 2720-2732. 

Lysosomal proteins are targeted to the lysosomes via the addition of a mannose 6-phosphate signal that is added in the ds-compartment of the Golgi and is recognized by a receptor protein in the frans-compartment of the Golgi. The protein is then transported by specialized vesicles to a late endosome that later matures into a lysosome. The mannose 6-phosphate receptor recycles back to the Golgi for re-use. 

D. P. Bottaro, S. Bonner-WfeJr, and G. L. King. Insulin receptor recycling in vascular endothelial cells, regulation by insulin and photbol ester. J. BtoL Chem. 264 5916 (I989X... 

The protocol can be adapted to measure receptor recycling. If radiolabeled antibodies are internalized into cells by incubation at 37°C in the presence of chemokine or other agents, the acid-elution procedure can be used to remove radiolabeled antibodies remaining on the cell surface. If the acid-elution medium is not reduced below pH 3.0, and the washes kept brief and performed at 4°C, then the cells can be returned to 37°C culture (care should be taken to ensure that the endocytic-trafficking properties of cells are not perturbed by the low pH treatment). During a subsequent incubation at 37°C, receptors that recycle will return antibodies to the cell surface. These antibody molecules can be assessed by measuring the radioactivity that becomes accessible to a second round of acid elution. 

Differences in Fc receptor y-chain transmembrane domains (particularly polar or charged residues among the C-terminal 11 amino acids) influence cell membrane receptor expression and function [91]. The charged residues might protect Fc RI and FcYRIIIa receptors during membrane-associated receptor recycling in proteasomes associated with the endoplasmic reticulum or other intracellular structures [91]. 

Sheff DR, Daro EA, Hull M, Mellman I. The receptor recycling pathway contains two distinct populations of early endosomes with different sorting functions. J Cell Biol 1999 145(l) 123-39. 

Enrich, C., Pol, A., Calvo, M., Pons, M., Jackie, St. Dissection of the multifunctional receptor-recycling endocytic compartment of hepatocytes. Hepatology 1999 30 1115-1120... 

Cong M, Perry SJ, Hu LA, Hanson PI, Claing A, Lefkowitz RJ. Binding of the fS2 receptor to n-ethylmaleimide-sensitive factor regulates receptor recycling. J Biol Chem 2001 276 45,145-45,152. 

An additional complexity is the possibility of protein-protein interactions during the cascade of receptor-recycling events. We now know that receptor subtypes can form oligomers, and this has become an area of great interest. The visualization of protein-protein interactions can be achieved using simple co-localization studies (15) or FRET (14). Co-localisation is a process whereby... 

Cong, M., Perry, S. J., Hu, L. A., Hanson, P. I., Claing, A., and Lefkowitz, R. J. (2001). Binding of the beta2 adrenergic receptor to N-ethylmaleimide-sensitive factor regulates receptor recycling.. Biol. Chem. 276, 45145 45152. 

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