Trafficking

Several aspects of intracellular trafficking should be kept in mind in the intracellular trafficking section. The first is the dependence of acidification of endosomes on the uptake of liposomes. This aspect is sometimes discussed when analyzing clathrin uptake. However, several other pathways are also in need of acidic compartments as a destination of uptake so, we list this factor as an individual aspect. Other aspects of intracellular trafficking that are of interest are the transport from early endosomes to late endosomes, the dependence of actin filaments and dynamin, and/or microtubules. Furthermore, the energy dependence of liposome uptake is discussed. 

Molecules entering cells through endocytic pathways will rapidly ( 2min) experience a drop in pH from neutral to pH 5.9-6.0 in the lumen of 

Because the intracellular pH at least partially regulates the intracellular sorting of endocytosed ligands (61), a block of acidification leads to a change of intracellular distribution and diminished uptake (82). 

Two different approaches are taken to prevent acidification (i) several substances are applied to block the acidification of endosomes by interfering with endosomal enzymes such as H(+)-ATPase and (ii) lysosomotropic reagents (generally weak bases) are known to accumulate within intracellular organelles and increase their pH. 

In both cases, the transport of some proteins to the lysosome is blocked, suggesting that acidification itself is required as part of this progress. Regarding their effect on transcytosis there is a difference between both groups. Although bafilomycin and chloroquine have only a small effect, the lysosomotropic substances (ammonium chloride and monensin) suppress transcytosis [mediated by clathrin (EGF) for details on transcytosis see section Transcytosis ] (61,106). 

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Anhydride has been used for the illegal manufacture of heroin [561-27-3] (acetyknorphine) and certain other addictive dmgs. Regulations on acetic anhydtide commerce have long been a feature of European practice. After passage in 1988 of the Chemical Diversion and Trafficking Act, there is also U.S. control. Orders for as much as 1,023 kg acetic anhydtide, for either domestic sale or export, require a report to the Department of Justice, Dmg Enforcement Administration (54). 

Physical evidence serves two purposes. In some cases it is used to prove a component or element of a crime. Eor example, in a case involving trafficking in cocaine [50-36-2] the prosecutor must prove that the white powder found in the criminal s possession was cocaine (Table 1). The forensic chemist tests the substance and issues a report. If the powder is methamphetamine [537-46-2] the charge must be amended. 

The large numbers of dmg trafficking arrests made by poHce agencies and the resulting high volume of cases submitted to most crime laboratories... 

Defects in the LDL receptor have been particularly well explored as a basis of the disease familial hypercholesterolemia (93,111). A number of defects that collectively impair LDL receptor trafficking, binding, or deUvery underHe this disease where LDL and semm cholesterol rise to levels that mediate early cardiovascular mortaUty. Studies of the population distribution of this defect can determine the source of the original mutation. Thus, in Quebec, about 60% of the individuals suffering from familial hypercholesterolemia have a particular 10-kdobase deletion mutation in the LDL gene (112). This may have arisen from an original founder of the French Canadian settiement in the seventeenth century. 

Are any materials subject to the provisions of the Chemical Diversion and Trafficking Act of 1988 ... 

D.L. Flynn, Phase-trafficking reagents and phase-switching strategies for parallel synthesis, Med Res Rev 19 408-431 1999. 

Watson, C., Chen, G., Irving, P. E., Way, J., Chen, W.-J., and Kenakin, T. P. (2000). The use of stimulus-biased assay systems to detect agonist-specific receptor active states Implications for the trafficking of receptor stimulus by agonists. Mol. Pharmacol. 58 1230-1238. 

Annexins form an evolutionary conserved family of Ca2+ and phospholipid binding proteins implicated in membrane trafficking and the regulation of Ca2+ currents across membranes. 

Mutations in two genes directly lead to a disease. Mutations in the AQPO gene lead to dominantly inherited cataract. Single amino acid substitution in the AQPO gene in both mice and humans result in proteins with impaired trafficking to the plasma membrane and cataract formation, due to loss of the integrity of the lens. 

Protein Trafficking and Quality Control Intracellular Transport Palmitoylation Endothelins... 

Constitutive exocytosis/secretion takes place in all eukaryotic cells and is essential for cell viability and growth. Trafficking vesicles destined for constitutive exocytosis originate from the trans-Golgi-network and contain secretory macromolecules derived from the... 

Moore CA, Milano SK, Benovic JL (2007) Regulation of receptor trafficking by GRKs and arrestins. Annu Rev Physiol 69 451-482... 

This experimental drug is a derivative of myriocin. After phosphorylation FTY720 modulates chemotactic responses and lymphocyte trafficking, leading to reversible lymphocyte sequestration in secondary lymphoid tissues. It is in clinical trials for the treatment of multiple sclerosis. 

GPI-anchored proteins constitute a quite diverse family of cell-surface molecules that participate in such processes as nutrient uptake, cell adhesion, and membrane signaling events [3]. All GPI-linked proteins are destined for the cell surface via trafficking through the secretory pathway, where they acquire the... 

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