Intracellular trafficking recycling

After transfer of heme to MHBP, either directly from hemopexin or from the hemopexin receptor, hemopexin and the receptor both recycle to the surface to undergo further rounds of transport. The heme inside the cell requires further intracellular trafficking to deliver heme to regulatory sites and to HO-1 for catabolism to biliverdin and iron, making intracellular transport an interesting focus of future research. The biliverdin is reduced and excreted as bilirubin, and the iron released, which can also have regulatory effects, is reutilized or stored on ferritin. 

Figure 11.1 The intracellular trafficking pathway of plasmid DNA complexed by poly cationic lipid (lipoplex). Critical steps are indicated by numbers (1) endocytosis, sorting and recycling via vesicular compartments comprising the early (EE) and sorting endosomes (2) entrapment and degradation in the late-endosomes (LE) and lysosomes (3) destabilization of the endo-lysosomal membrane and release into the cytosol, (the precise location of this step is not known) (4) diffusion toward the nuclear pore complex (NPC) and degradation in the cytoplasm, and (5) nuclear translocation across the NPC.

Presently, it cannot be excluded that despite the apparently highly specific function of certain Rabs in intracellular trafficking pathways there is redundancy with respect to vesicle docking in the synapse. The surprising diversity of Rabs on highly purified synaptic vesicles (more than 30 different Rabs) supports the view that multiple Rabs are required for synaptic vesicle recycling, which may have overlapping functions. 

Upon activation, neurons begin trafficking TRPVl to the membrane where the receptors become activated, desensitized and then recycled to the intracellular compartments. Translocation of TRPVl to the cell membrane occurs via SNARE (snapin and synaptotagmin IX)-mediated exocytosis [37]. Broadly speaking, activation involves phosphorylation by protein kinases (most notably, protein kinase A [PKA] and C [PKC]) and desensitization involves de-phosphorylation by phosphatases (e.g. calcineurin) [38]. Among PKC isozymes, PKCp seems to be of particular importance [39]. 

The desensitization motifs in the dopamine Dj receptor, as an example, may be at least partly located in the proximal carboxyl tail of the receptor f/22). This region may interact with portions of the third intracellular loop to promote desensitization. These structures may also be involved in recycling and trafficking of inactivated receptors (147). 

The desensitization motifs in the dopamine Di receptor, as an example, may be at least partly located in the proximal carboxyl tail of the receptor [137], It is likely that this region interacts with portions of the third intracellular loop in order to promote desensitization. These structures may also be involved in recycling and trafficking of inactivated receptors [162, 163], A portion of the proximal carboxyl tail of the dopamine Di receptor may contain some of the residues necessary, but not sufficient on their own, for GRK2 mediated desensitization. A motif consisting of a serine or threonine preceded by an acidic amino acid may define the GRK2 recognition sequence [163],... 

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.)...

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