Endocytic recycling pathway

Jones, M.C., Caswell, P.T., and Norman, J.C. (2006). Endocytic recycling pathways emerging regulators of cell migration. Curr Opin Cell Biol 18 549-557. 

The information available at present implies that GPI-anchored proteins are sorted in unique ways in both the exocytic and endocytic pathways. Detergent-insoluble membrane rafts containing cholesterol and sphingolipids may aid in the sorting of GPI-anchored proteins in the trans Golgi network as well as play a role in their slow rate of endocytic recycling. 

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.

There are also multiple pathways for liposomes following cellular uptake. They may be delivered to lysosomes, recycled out of the cell, involved in transcytotic passage across an epithelial barrier, or delivered to other cellular compartments such as the Golgi network. Each route offers opportunities for selective delivery of macromolecular drugs and nanosized drugs so the need to comprehend endocytic pathways has never been more apparent (7). Figure 1 summarizes the different pathways of endocytosis. 

Early endosomes are the main sorting station in the endocytic pathway. In their acidic interior (pH 5.9-6.0), the receptor and its ligand can be released. The receptor may be recycled to the surface by vesicles that fuse with the plasma membrane. Material that cannot escape from the early endosomes is further transported via multivesicular bodies to late endosomes and digesting lysosomes that contain a broad spectrum of peptidases and hydrolases in an acidic surrounding [for reviews on endocytosis see Refs. (10-12), for review on clathrin uptake see Refs. (9,13)]. 

Virmani T, Han W, Liu X, Sudhof TC, Kavalali ET (2003) Synaptotagmin 7 splice variants differentially regulate synaptic vesicle recycling. EMBO J 22 5347-57 Voglmaier SM, Kam K, Yang H, Fortin DL, Hua Z, Nicoll RA, Edwards RH (2006) Distinct endocytic pathways control the rate and extent of synaptic vesicle protein recycling. Neuron 51 71-84... 

Fig. 5 Synaptic vesicle recycling in the synapse. For synaptic vesicle recycling, several endocytic mechanisms appear to co-exist in synaptic nerve terminals. In the case of fast kiss-and-ran exo-cytosis/endocytosis, the fused vesicle does not collapse into the membrane but is retrieved directly by a fast process. The molecular machinery underlying this pathway is unknown. Vesicles that have fully collapsed into the membrane are recycled by clathrin-mediated endocytosis. Clathrin, along with other proteins, is involved in membrane invagination (see figure and text) and leads finally to the formation of a constricted pit. The GTPase dynamin (black ring) mediates membrane scission of the constricted pit. After removal of the clathrin coat, two pathways are possible (direct recycling and recycling via the early endosome). In all cases, before fusion the recycled vesicles have to be loaded with neurotransmitters (NT).

Voglmaier SM, Kam K, Yang H, Fortin DL, Hua Z, et al. 2006. Distinct endocytic pathways control the rate and extent of synaptic vesicle protein recycling. Neuron 51 71-64. 

The internalization of Tf occurs via an endocytotic clathrin-coated process, and the internalization signal YTRF is also recognized by clathrin lattices in the trans-Golgi (127). In vitro studies have indicated that there are two different endocytic pathways of clathrin-coated vesicles in cells a short-term (10-20 min) recycling... 

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