Transport mechanisms trafficking

Virtually all that is known regarding the transport and trafficking of manganese has come ft om studies in yeast and it is anticipated that similar mechanisms exist in higher eukaryotes including humans. Manganese that originates in the extracellular environment is first taken up by the cell via... 

In this section, we provide an overview of the physical characteristics of nanomaterials that enable them to interact with animal cells and cellular compartments. Because they are chemically stable and relatively inert, 1-D nanostructures (1-D NS) have relatively low cell cytotoxicity (as outlined above), while their chemical modification also provides a means for linkage with specific biomolecules. Thus, 1-D NS may interact directly with cellular substructures. In addition, a typical cellular targeted delivery strategy is also discussed that can support the cellular uptake of these nanoshuctures. Notably, 1-D NS with dimensions of 2 to lOOnm are particularly suited to the adoption of intrinsic cellular transport mechanisms, and can be used for the targeted delivery of specific biomolecules to specific cells and tissues. Moreover, 1-D NS may also provide nanoplatform constructs for the delivery of specific biomolecules through interactions in well-characterized intracellular trafficking pathways. 

Protein trafficking is the transport of proteins to their correct subcellular compartments or to the extracellular space ( secretory pathway ). Endo- and exocytosis describe vesicle budding and fusion at the plasma membrane and are by most authors not included in the term protein trafficking. Protein quality control comprize all cellular mechanisms, monitoring protein folding and detecting aberrant forms. 

Recent evidence indicates that the 5-HT transporter is subject to post-translational regulatory changes in much the same way as neurotransmitter receptors (Blakeley et al. 1998). Protein kinase A and protein kinase C (PKC), at least, are known to be involved in this process. Phosphorylation of the transporter by PKC reduces the Fmax for 5-HT uptake and leads to sequestration of the transporter into the cell, suggesting that this enzyme has a key role in its intracellular trafficking. Since this phosphorylation is reduced when substrates that are themselves transported across the membrane bind to the transporter (e.g. 5-HT and fi -amphetamine), it seems that the transport of 5-HT is itself linked with the phosphorylation process. Possibly, this process serves as a homeostatic mechanism which ensures that the supply of functional transporters matches the demand for transmitter uptake. By contrast, ligands that are not transported (e.g. cocaine and the selective serotonin reuptake inhibitors (SSRIs)) prevent the inhibition of phosphorylation by transported ligands. Thus, such inhibitors would reduce 5-HT uptake both by their direct inhibition of the transporter and by disinhibition of its phosphorylation (Ramamoorthy and Blakely 1999). 

Lipids are transported between membranes. As indicated above, lipids are often biosynthesized in one intracellular membrane and must be transported to other intracellular compartments for membrane biogenesis. Because lipids are insoluble in water, special mechanisms must exist for the inter- and intracellular transport of membrane lipids. Vesicular trafficking, cytoplasmic transfer-exchange proteins and direct transfer across membrane contacts can transport lipids from one membrane to another. The best understood of such mechanisms is vesicular transport, wherein the lipid molecules are sorted into membrane vesicles that bud out from the donor membrane and travel to and then fuse with the recipient membrane. The well characterized transport of plasma cholesterol into cells via receptor-mediated endocytosis is a useful model of this type of lipid transport. [9, 20]. A brain specific transporter for cholesterol has been identified (see Chapter 5). It is believed that transport of cholesterol from the endoplasmic reticulum to other membranes and of glycolipids from the Golgi bodies to the plasma membrane is mediated by similar mechanisms. The transport of phosphoglycerides is less clearly understood. Recent evidence suggests that net phospholipid movement between subcellular membranes may occur via specialized zones of apposition, as characterized for transfer of PtdSer between mitochondria and the endoplasmic reticulum [21]. 

This convention specifies guidelines and mechanisms for international cooperation in fighting narcotics trafficking, including conduct of multinational law enforcement operations. It specifies standards that signatory nations should enact into law regarding such matter as the manufacture, import, export, and transportation of controlled substances. 

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