Vesicular trafficking

Disorders caused by the impairment of the Golgi apparatus and further vesicular trafficking (e.g., mutations in the Rab escort protein Repl leading to choroideremia). 

Tight junctions (up to 2 nm) with continuous basement membrane extravasation mainly by vesicular trafficking... 

Hanada, K., Kumagai, K., Yasuda, S. et al. 2003. Molecular machinery for non-vesicular trafficking of cer-amide. Nature, 426(6968) 803-809. 

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]. 

Some intracellular signal transduction molecules are reduced in schizophrenia. The release of neurotransmitters is regulated by a family of proteins that coordinate vesicular trafficking (see Ch. 9). Of these, the expression of complexin I and II appears to be decreased in prefrontal cortex and subfields of the hippocampal formation, and the ratio of complexin I to complexin II is elevated in the hippocampus [35], SNAP-25 (Synaptosomal Associated Protein, kDa 25) has inconsistently been found to be down-regulated in both these regions. Synapsin expression is also reduced, but more robust decrements have been observed in bipolar disorder (Ch. 55). 

Vesicular trafficking and inclusion body formation are both dependent on the integrity of microtubules and other cytoskeletal components. Parkin has been shown to target misfolded tubulin for degradation [251] (figure 4.6B) and to interact with centrosomes upon proteasomal inhibition [252]. Whether this reflects association with specific substrates or co-localization with proteasomes in centrosomes re-... 

Melendez, A., Floto, R.A., Gillooly, D.J., Harriett, M.M and Allen, J.M., 1998, FcyRI coupling to phospholipase D initiates sphingosine kinase-mediated calcium mobilization and vesicular trafficking, J. Biol. Chem. 273 9393-9402. 

Pavlov, N.J., Xu, J., Riedel, D., Yeoh, J.S., Teitelbaum, S.E., Papadimitriou, J.M., Jahn, R., Ross, F.P., and Zheng, M.H. (2005) Rab3D Regulates a Novel Vesicular Trafficking Pathway That Is Required for Osteoclastic Bone Resorption. Molecular Cell Biology li, 5253-5269. 

Neuropathology of Alzheimer s is also defined by accumulation of another form of insoluble protein, the neurofibrillary tangles (NFTs). NFTs are fibrillar structures largely composed of tau, a microtubule-binding protein that stabilises the microtubule tracts necessary for vesicular trafficking, endo- and exocytosis and axonal polarity. No tau mutations have yet been identified... 

More recent evidence suggests a role in intracellular vesicular trafficking (Caviston and Holzbaur, 2009). HD is the most common of the (CAG)n/Qn-expansion diseases, despite the fact that new expansion mutational expansions in the Htt gene are believed to be exceedingly rare. The incidence of HD worldwide is about 5-10 per 100,000 individuals. Japan has a very low rate (0.1-0.5 per 100,000), whereas in the Lake Maracaibo region of Venezuela the incidence exceeds 100 per... 

Caviston IP, Holzbaur EL (2009) Huntingtin as an essential integrator of intracellular vesicular trafficking. Trends Cell Biol 19 147-155... 

Cell membranes are two-dimensional fluids that exhibit a wide range of dynamic behaviors. Recent technical advances have enabled unprecedented views of membrane dynamics in living cells. In this technical review, we provide a brief overview of three well-studied examples of membrane dynamics lateral diffusion of proteins and lipids in the plane of the membrane, vesicular trafficking between intracellular compartments, and exchange of proteins on and off membranes. We then discuss experimental approaches to monitor membrane protein and lipid dynamics, and we place a special emphasis on the use of genetically encoded fluorescent probes and live cell-imaging techniques. 

Figure 5 Proteomics reveals functional secretory vesicle protein systems for neuropeptide biosynthesis, storage, and secretion. Chromaffin secretory vesicles (also known as chromaffin granules) were isolated and subjected to proteomic analyses of proteins in the soluble and membrane components of the vesicles. Protein systems in secretory vesicle function consisted of those for 1) production of hormones, neurotransmitters, and neuromodulatory factors, 2) generating selected internal vesicular conditions for reducing condition, acidic pH conditions maintained by ATPases, and chaperones for protein folding, and 3) vesicular trafficking mechanisms to allow the mobilization of secretory vesicles for exocytosis, which uses proteins for nucleotide-binding, calcium regulation, and vesicle exocytosis. These protein systems are coordinated to allow the secretory vesicle to synthesize and release neuropeptides for cell-cell communication in the control of neuroendocrine functions.

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