Endosome recycling internalization into endosomes

Nanoparticles that are internalized into cells by these mechanisms first enter the primary endosomes of the cell and are then transported into sorting endosomes. While some nanoparticles in the sorting endosomes are transported out of the cell by recycling endosomes, the remaining nanoparticles are transported into secondary endosomes that fuse with the lysosomes [107].The surface charge of PLGA nanoparticles is reversed in the acidic lysosome, resulting in their escape into the cytoplasm... 

Internalization of a receptor can occur after activation, GRK-mediated phosphorylation, and recruitment of P-arrestins. In consequence, receptors are removed from the cell surface by internalization into endosomes. The further faith of the receptor will either be degradation after sorting to lyso-somes, or rescue and recycling back to the cell surface. In any case, this intemahzation event leads to desensitization of the ceU toward the receptor s ligands (Marchese, 2014 Marchese, Paing, Temple, Trejo, 2008 Vroon, Heijnen, Kavelaars, 2006). 

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.

It should be pointed out, however, that not all hormones dissociate from their receptor in the pH 5.5 environment of the endosome [24], Some hormone-receptor complexes require much lower pH values for dissociation to occur. Although not a peptide hormone, the iron-transport protein transferrin is a peculiar example of this phenomenon and should be pointed out. In this case, at the neutral pH of the extracellular fluid transferrin containing bound iron binds to its cell surface receptor and is internalized. In the low pH environment of the endosome, iron becomes dissociated from transferrin, but transferrin remains bound to its receptor. The transferrin receptor, with bound transferrin, is then recycled to the cell surface. With iron no longer bound to the transferrin, the transferrin readily dissociates from its receptor at the neutral pH of the extracellular fluid [25,26]. This mechanism provides for an efficient continual uptake of iron into cells. Unlike transferrin, however, in those instances where peptide hormones have been documented not to be dissociated from their receptor in the endosome compartment, the hormone and receptor are delivered to the lysosomes via fusion of the endosomes with lyso-somes, where both hormone and receptor are degraded [24,27]. The continuous degradation of the receptor with each round of RME eventually leads to a decrease in the number of receptors on the cell surface, a phenomenon called down-regulation. 

Figure 1 Overview of the synaptic vesicle cycle, (a) Within the presynaptic terminal, synaptic vesicles are filled with neurotransmitter by the action of specific vesicular neurotransmitter transporters, (b) Neurotransmitter-filled vesicles translocate to the active-zone membrane where they undergo docking, (c) Docked vesicles transition to a release-competent state through a series of priming or prefusion reactions, (d) Invasion of an action potential into the presynaptic terminal and subsequent calcium influx induces rapid fusion of the synaptic vesicle membrane with the terminal membrane, which thereby releases the neurotransmitter into the synaptic cleft, (e) Spent vesicles are internalized by clathrin-mediated endocytosis and are recycled for reuse, which thus completes the synaptic vesicle cycle. SV, synaptic vesicle CCV, clathrin-coated vesicle EE, early endosome. NOTE The use of arrows indicates a temporal sequence of events. Physical translocation of synaptic vesicles is unlikely to occur between the docking and fusion steps.

Figure 8.4. Intracellular sorting pathways of RME. The initial binding and uptake steps [including receptor clustering in eoated or noncoated pits, internalization of the receptor-ligand complex into coated vesicles (noneoated in the ease of potoc3d osis), and fusion of vesicles to form endosomes] are common to all pathways. After entry into acidic endosomes, ligand and receptors are sorted and trafficked independently, whieh may result in degradation, recycling or transcytosis of either molecule (seetext). L, ligand R, receptor lysosomes are depicted as shaded circles. (Adaptedfrom Ref 10.)...

Several sources of cellular cholesterol contribute to RCT. Part of the process of RCT reflects peripheral (extra-hepatic) cholesterol synthesis. Despite the down-regulation of cholesterol synthesis mediated by the LDL receptor via the delivery of LDL, a considerable amount of sterol is made in peripheral tissues. The importance of this source of cholesterol to homeostasis may be as great as that of dietary cholesterol in many individuals. After hydrolysis of LDL-CE by cellular cholesterol esterases, this cholesterol is made available for recycling to the cell surface and can be recovered there by apo A1 for incorporation into HDLs. Cholesterol is also available from VLDLs, LDLs, and chylomicrons directly internalized by peripheral cells. Cholesterol from HDLs bypasses the lysosomal pathway and becomes part of recycling endosomes that return to the cell surface. Some of the cholesterol recovered on HDLs originates from blood cells. Finally, some cholesterol is transferred directly to other lipoproteins from chylomicrons, VLDLs, and LDLs, without entering the cell. 

---