Endocytosis, schematic

Figure 11.1 Schematic representation of iron uptake mechanisms, (a) The transferrin-mediated pathway in animals involves receptor-mediated endocytosis of diferric transferrin (Tf), release of iron at the lower pH of the endocytic vesicle and recycling of apoTf. (b) The mechanism in H. influenzae involves extraction of iron from Tf at outer membrane receptors and transport to the inner membrane permease system by a periplasmic ferric binding protein (Fbp). From Baker, 1997. Reproduced by permission of Nature Publishing Group.

Fig. 3.5 Schematic flow-chart of antibody degradation by proteases combined with the protection by Fc-Rn in phagosomes. (1) IgG molecules are transported to the extracellular space (= interstitial fluid). (2) IgG molecules enter a cell by receptor-mediated endocytosis where the Fc region of the antibody is bound to the limited binding sites of Fc-Rn.

An important question is how to achieve the most efficient delivery of PNA. This problem does not usually have a definite answer and many different factors must be considered. Table 1 reviews the main types of PNA-peptide conjugates and indicates the most important issues in each case. The internalization routes are schematically drawn in Fig. 2. Depending on the peptide attached, the PNA oligomer is internalized via endocytosis or directly delivered across the cell membrane. For nuclear localization signals (NLS) and tetralysine (K4) the delivery route is not clear yet. The same holds true for nuclear delivery with CPPs. Some CPPs (e.g., transportan) have been shown to accumulate in the nucleus, while others have not. 

Fig. 6 Schematic depiction of cellular uptake mechanisms fluid-phase endocytosis, receptor-mediated endocytosis, and transc5dosis. (Illustration by Leigh A. Rondano, Boehringer Ingelheim Pharmaceuticals, Inc.)...

Figure 3.1 (Top ) Schematic view of processes controlled by curvature in endocytosis. Adapted from [2]. (Bottom ) Representative of the simplest surfactant aggregates spherical micelles v/al between 1/3 (spheres) and 1/2 (cylinders) planar bilayers (v/al = 1) inverted micelles...

Fig. 8. Schematic diagram illustrating various pathways of endocytosis (1) phagocytosis, (2) receptor-mediated phagocytosis, (3) pinocytosis, and (4) receptor-mediated pinocytosis...

T3) within the protein backbone of the thyroglobuiin protein in the follicular lumen. Endocytosis followed by proteolytic cleavage of thyroglobuiin releases the iodothyronines into the circulation. A schematic outline of iodine metabolism, with emphasis on the formation and secretion of thyroid hormones, is shown in Figure 52-3. 

Figure 4.8 Schematic drawing of the mechanisms and routes of drug absorption across intestinal epithelia. Drugs can be absorbed transcellularly [1) and paracellularly (2) by passive diffusion or transcellularly via carrier-mediated transport [3) or endocytosis C4). Enzymes in the brush-border region or intracellular enzymes and the efflux proteins, e.g., P-glycoprotein (5) contribute to the elimination of harmful compounds.

Fig. 8.6 Schematic diagram iiiustrating the intra-ceiiuiar pharmacokinetic modei of the exogenous DNA. The intraceiiuiar disposition of the gene is represented. A compiex of DNA and gene vector is internaiized via endocytosis Endosomai...

Studies of this type have provided evidence for several different cellular pathways of CE metabohsm (see also Chapter 2). A major pathway, typical of cells such as fibroblasts [97], is shown schematically in Fig. 1. Plasma lipoproteins that contain CE and apohpoproteins B and/or E adsorb to specific apohpoprotein receptors on the cell surface, and are subsequently internalized by receptor-mediated endocytosis. Endocytotic vesicles containing the hpoproteins then fuse with lysosomes, whose enzymes catalyze lipoprotein hydrolysis. Lysosomal acid CEH catalyzes the hydrolysis of lipoprotein CE. The UC released then transfers across the lysosomal membrane and becomes available for synthetic processes within the cell. Excess UC entering the cytoplasm is converted into CE by the ACAT reaction, but can be released upon demand through the action of neutral CEH. 

Figure 5.18 Receptor-mediated endocytosis. (a) Schematic diagram of the main steps in the endocytotic pathway. Binding at the cell surface induces clustering of receptor-ligand complexes in specialized regions of the membrane. Endocytotic vesicles form in these regions separation of receptor and ligand occurs as the endosome matures. Separated receptors can recycle to the surface, while remaining material is degraded within lysosomes. (b) Typical time course of internalization and degradation.

Fig. 6.35. Schematic representation of possibie modes of interaction of iiposomes with ceiis that iead to intraceiiuiar deiivery. Liposomes can enter the ceii by iocai destabiiization of piasma membrane or fusion (a) or endocytosis (b). The reieases of DNA by fusion is stiii not ciear (c or d). The reieased DNA or cationic iiposome-DNA compiexes reach into the nucieus (e), and gene expression occurs (f). (Adapted from Singhai A, Huang L.Gene transfer in mammaiian ceiis using iiposomes as carriers. In Wolff JA, ed. Gene Therapeutics. Boston Birkhauser, 1994 118 with permission.)...

Fig. 5 Schematic diagram of the siRNA delivery system. A cationic group is universal in all siRNA delivery systems to condense siRNA into nanosized complex. To release the siRNA from the endosome after endocytosis, an endosomal disrupting agent is also essential. PEG modification is also important to improve the pharmacokinetic profile of the complex, as well as to avoid the nonspecific uptake by RES. To achieve the targeted delivery to tumor cells, various ligands including antibody, antibody fragments, peptides, small molecules should be modified to the complex directly or via PEG as a linker...

Figure 1 Schematic of polycadon-pDNA binding, polyplex formation, and cellular deliveiy. (a) Polycations bind with pDNA via electrostatic interactions, (b) Smail nanoparticies (polyplexes) spontaneously form that associate with the cellular membrane, (c) Upon glycoprotein binding, polyplexes are internalized via endocytosis. (d) Endosomes carry the polyplexes into the cells, (e) The polyplexes must escape the endosomes to avoid degradation, (f) The polymeric delivery vector must reiease Its nucleic add cargo either in the cytoplasm or in the nucleus (depending in the desired destination) for effective delivery. It should be noted that delivery of other nucleic acid forms (i.e., siRNA) is thought to occur by similar pathways. Adapted from Reineke. T. M. J. Pofym. Sci. A Polym. Chem. 2006, 44,6895. ...

Figure 37 Schematic representation of stimuli-responsive polymer nanocapsules formed from covalent cross-linking of functional CB[6] developed by Kim efa/. The CB[6] allows facile supramolecular conjugation of targeting moieties for cellular receptor-mediated endocytosis. Reproduced from Kim, E. Kim, D. Jung, H. etal. Angew. Chem. Int Ed. 2010, 49,1-5. ...

Figure 6.10 Schematic showing transfection of plasmid DNA into a cell via endocytosis using a block polyelectrolyte. [S. Forster and M. Konrad, J. Mater. Chem., 13, 2671-2688. Copyright (2003) - Reproduced by permission of the Royal Society of Chemistry]...

Figure 1. Schematic representation of HIV-1 depicting oligosaccharides of the envelope glycoprotein gp 120 (A), and binding of high mannose type V-glycans to the macrophage endocytosis receptor (B). (Taken from [1] with permission.)...

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