Clathrin-coated pit

Arrestins act as adaptor proteins that bind to phos-phorylated G protein-coupled receptors (GPCR) and link the receptors to clathrin-coated pits. (3-Arrestins are essential in the internalization of many GPCRs. 

A process in which a substance gains entry into a cell. Endocytic mechanisms are crucial for a variety of cellular functions such as the uptake of nutrients, regulation of cell surface expression of receptors, maintenance of cell polarity, and more. Receptor-mediated endocytosis via clathrin-coated pits is the most studied endocytic process, which is important for regulation of the time and magnitude of signals generated by a variety of cell-surface receptors. 

Clathrin-coated Pits Clathrin-coated Vesicle CLC... 

Heterologous desensitisation refers to the desensitisation of the response to one agonist by the application of a different agonist. For example, desensitisation of a response to adrenaline by application of 5-HT is mediated by protein kinase A or protein kinase C because these kinases can phosphorylate receptors which are not occupied by agonist. Phosphorylation disrupts the receptor-G-protein interaction and induces the binding of specific proteins, arrestins which enhance receptors internalisation via clathrin-coated pits. Thus desensitisation of G-protein-coupled receptors results in a decrease in the number of functional receptors on the cell surface. 

Cvejic et al. [133] and Trapaidze et al. [134] have reported that the C-terminus of the 8 receptor is essential for the internalization and downregulation of the receptors. Truncation of the 8 receptor attenuates receptor internalization. Residue Thr353 seems to be selectively involved in the internalization of the receptor, since mutation of this amino acid blocks the internalization process. Recent studies by Chu et al. [135] not only confirm the role of the C-terminus in internalizing the 8 receptor but have shown that clathrin-coated pits are involved in the internalization since a K44I mutant of dynamin I blocks the rapid internalization of the 8 receptor. These studies have identified a structural basis for the differential regulation of the three opiate receptors. 

In the classic model of synaptic vesicle recycling in nerve terminals, synaptic vesicles fuse completely with the plasma membrane and the integrated vesicle proteins move away from the active zone to adjacent membrane regions (Fig. 9-9A). In these regions, clathrin-mediated synaptic vesicle endocytosis takes place rapidly after neurotransmitter release (within seconds) [64]. The process starts with the formation of a clathrin-coated pit that invaginates toward the interior of the cell and pinches off to form a clathrin-coated vesicle [83]. Coated vesicles are transient organelles that rapidly shed their coats in an ATP/chaperone dependent process. Once uncoated, the recycled vesicle fuses with a local EE for reconstitution as a synaptic vesicle. Subsequently, the recycled synaptic vesicle is filled with neurotransmitter and it returns to the release site ready for use. This may be the normal pathway when neurotransmitter release rates are modest. Clathrin/ EE-based pathways become essential when synaptic proteins have been incorporated into the presynaptic plasma membrane. 

Both intracellular depletion of potassium and hypertonic treatment lead to disruption of clathrin from the inner side of the plasma membrane. Consequently, the formation of clathrin-coated pits and clathrin-coated vesicles is... 

Clathrin uptake can be inhibited by anticlathrin heavy chain antibodies. When applied to the cells, they lead to aggregation of clathrin in the cytoplasm and reduce the number of clathrin-coated pits on the plasma membrane (49). 

Shiga toxin is described as being transported after uptake via clathrin-coated pits from recycling endosomes to the Golgi apparatus (31). 

After attachment to the cell surface, the virus is located in clathrin-coated pits and is further internalized by an endocytosis similar to the receptor-mediated endocytosis of LDL (114,115). 

Uptake of SV40 occurs specifically by the caveolar pathway. Less than 5% of internalized particles are found to pass through clathrin-coated pits (26). Even though SV40 was known to be a highly specific marker for caveolae uptake, the virus is now described as entering the cells via a different mechanisms (121). 

Heuser JE, Anderson RG. Hypertonic media inhibit receptor-mediated endocy-tosis by blocking clathrin-coated pit formation. J Cell Biol 1989 108(2) 389-400. 

Subtil A, Gaidarov I, Kobylarz K, Lampson MA, Keen JH, McGraw TE. Acute cholesterol depletion inhibits clathrin-coated pit budding. Proc Natl Acad Sci USA 1999 96(12) 6775-6809. 

Eord MGL, Mills IG, Peter BJ, Vallis Y, Praefcke GJK, McMahon HT. Curvature of clathrin-coated pits driven by epsin. Nature 2002 419(6905) 361-366. 

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