Lysosomes, receptor interactions with

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.

Fig. 5.4 Endocytosis of GPCRs mediated by GRKs, arrestins and clathrin-coated pits. Receptor phosphorylation mediates recruitment of arrestins from the cytoplasm, the arres-tin interaction with other adaptotor proteins, and promotes receptor endocytosis by clathrin-coated pits. Internalised receptors may be sorted into a rapid recycling pathway, or to a degradative pathway into the lysosomes...

Many drugs function by interacting with their receptors inside the target cells, which are highly compartmentalized with multiple biomembranes such as the plasma membrane, the endoplasmic reticulum (ER), the endosomal/lysosomal membranes, and the nuclear envelope. 

The pharmacokinetics of efalizumab are highly influenced by the target expression, indicating the presence of a receptor-mediated clearance pathway [81-83]. Using purified mouse and human T cells, internalization of anti-CDlla antibodies was observed following interaction with CDlla. Internalized antibodies moved in endosomes to lysosomes and were catabolized within the cells [84, 85]. 

Growth factors are active at very low concentrations, i.e. about 1 pM. They exert their effect by binding to specific cell surface receptors with very high affinity. Related factors show lower affinity for the receptors of other members of the group. Following interaction with its receptor, the growth factor is internalised and transported via endocytotic vesicles to the lysosomal compartment where... 

Fig. 1. A model for the control of the luteinizing hormone receptor. LH interacts with a specific receptor (RLh) in Leydig cells which results in the activation of several transducing systems. This is followed by an uncoupling (desensitization) from one or more of the transducing systems. The latter may transiently remain active. The LH receptor complex is internalized and then dissociated in endocytic vesicles. LH is degraded in the lysosomes. The LH receptor synthesis can be controlled by several hormones including oestradiol, prolactin and growth hormone.

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