Distribution and Mobility of Receptors in the Plasma Membrane*
Sek Wen Hui in Freeze-Fracture Studies of Membranes, 1989
Coated pits appear in electron micrographs of thin sections as indentations in the plasma membrane about 200 nm in diameter. The cytoplasmic side of the membrane of the coated vesicles is differentiated as a lattice composed primarily of a protein called clathrin.39 Freeze-fracture replicas of cell membranes of cultured fibroblasts affirm that the coated pits are specialized regions of the membrane. The intramembranous particles of coated pits differ markedly in number and size from those of the remaining membrane. Since coated pits are difficult to identify in overviews of normal membrane fracture faces, we employed the polyene antibiotic filipin to aid in differentiating these structures. Typical filipin-sterol complexes are abundant on the plasma membrane fracture faces of filipin-treated fibroblasts (for details see Severs and Robenek40 and references therein). The complexes are completely absent in coated pits.41 The freeze-fracture technique is well suited for exposing large membrane areas, and the use of filipin for differentiating coated pits permits the study of the distribution of the coated pits on fracture faces of the plasma membrane, even at low magnification.19,41 With the aid of this technique, it is possible to show that coated pits are scattered randomly over the surface of the plasma membrane. The number of coated pits differs from cell to cell. They usually occur singly, but may also be found in groups of up to ten closely packed units (Figure 5a).
Absorption of Macromolecules by Mammalian Intestinal Epithelium
Shayne C. Gad in Toxicology of the Gastrointestinal Tract, 2018
Coated pits and vesicles are involved in receptor-mediated endocytosis.17,50 Clathrin, with a molecular weight 180,000, is the major structural protein of coated pits and vesicles.50,54 Clathrin defines the cytoplasmic side of endocyotic organelles by enclosing them in a lattice of pentamers and haxamers. Finally, a polyhedral vesicle is produced. In receptor-mediated endocytosis, it is believed that specific protein receptors are randomly dispersed in the lipid bilayer of the plasmalemma.49 To initiate internalization, the macromolecule or the ligand binds to its receptor. This in turn promotes the binding of clathrin to the other end of the receptor next, ligand-receptor-clathrin complexes cluster at the base of the microvillus, causing the plasmalemma to invaginate or pit. The coated pit pinches off forming a coated submicroscopic vesicle that then traverses the cell and fuses with the basal lateral membrane. Finally, the microvesicle undergoes reverse pincocytosis (exocytosis), resulting in the discharge of the ligand into extracellular space.70,72
Growth Factor Receptors
Enrique Pimentel in Handbook of Growth Factors, 2017
Receptor-mediated endocytosis has been classified into four categories, based on the final destination of both receptor and ligand.55 In the class I category, receptor and ligand dissociate from one another and the receptor is recycled to the cell surface whereas the ligand is degraded in lysosomes. In the class II category, receptor and ligand both recycle to plasma membrane. In the class III category, both receptor and ligand are transported to lysosomes. Finally, in the class IV category the ligand-receptor complexes are delivered to the opposite sides of polarized cells in a process referred to as transcytosis, the ligand is released intact on the opposite side of the membrane, and the receptor is either degraded or recycled. Despite the heterogeneity of receptors, the initial step of endocytosis for all four classes of cell surface receptors is the same: the ligand-receptor complex is internalized via clathrin-coated pits. When clathrin-coated pits are saturated with receptors, they invaginate, forming a clathrin-coated vesicle. These vesicles lose their clathrin and undergo an acidic shift in pHi resulting in an endosome.
Human ovarian granulosa cells use clathrin-mediated endocytosis for LDL uptake: immunocytochemical and electron microscopic study
Published in Ultrastructural Pathology, 2023
Aynur Abdulova, Merjem Purelku, Hakan Sahin, Gamze Tanrıverdi
Regarding the clathrin-mediated endocytic pathway, an important component is the clathrin protein. Clathrin-coated vesicles have a three-layered structure consisting of an outer region formed by clathrin proteins in the form of a cage, an intermediate region consisting of a lipid membrane, as well as internal adaptor proteins (APs).8 Along with clathrin, more than 60 other cytosolic proteins are involved in the formation of clathrin-coated endocytic vesicles.9 All these proteins assemble from the cytosol to the endocytic region in a highly ordered manner. The collected vesicles are transported to the target site by SNARE (N-ethylmaleimide-sensitive factor binding protein receptor) proteins. SNAREs manage the transfer of material to be transported during vesicular transport. In an animal cell, there are at least 20 different organelle-associated SNARE proteins, each attached to a specific membrane involved in the biosynthetic-secretion or endocytic pathway. These proteins function as transmembrane proteins and are referred to as vesicular SNAREs (v-SNAREs) with characteristic spiral domains.10
The roles of epidermal growth factor receptor in viral infections
Published in Growth Factors, 2022
Activated EGFR are rapidly internalised and ligand-induced endocytic trafficking is important in regulating duration and intensity of signal transduction. Clathrin-mediated endocytosis (CME) is a major mechanism of EGFR internalisation. Activated receptors are recruited into clathrin-coated pits which are further invaginated and pinched off as clathrin-coated vesicles. Once endocytosed, receptor-containing vesicles are uncoated and fuse with early endosomes. In early endosomes, the internalised receptors are either recycled to the cell surface or taken up into intraluminal vesicles which eventually lead to the delivery of EGFR to lysosome for degradation (Goh et al. 2010). Trafficking of receptors to lysosomal degradation results in signal attenuation, whereas receptors that are recycled can be re-stimulated by ligands that present. The endocytic routes of EGFR are depending on the types of ligands bound (Burke, Schooler, and Wiley 2001). Stimulations of EGF, HB-EGF and BTC lead to lysosomal degradation of EGFRs, whereas stimulations of AR, TGF-α and EPI lead to receptor recycling (Roepstorff et al. 2009).
Low-density lipoprotein nanomedicines: mechanisms of targeting, biology, and theranostic potential
Published in Drug Delivery, 2021
Under normal conditions, the receptor-mediated endocytosis of LDL occurs when ApoB-100 from LDL binds to LDLR and forms a complex embedded in clathrin-coated pits and vesicles (Figure 1) (Nykjaer & Willnow, 2002). The complex in the clathrin-coated pit subsequently separates from the cell membrane, forms a coated vesicle that depolymerizes its tubules to become an endosome, and fuses with sorting vesicles (i.e., late endosomes). During the maturation of endosomal compartments, a decrease in luminal pH (as low as pH 5) results in the dissociation of LDL from the LDLR. LDLR is then recycled back to the cell membrane, and LDL is catabolized into amino acids and free cholesterol, which is stored in the cells and in turn downregulates the expression of LDLR on the cell surface (Bareford & Swaan, 2007).
Related Knowledge Centers
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- C-Terminus
- N-Terminus