Vesicles membrane trafficking

Bennett, M., Scheller, R. A molecular description of synaptic vesicle membrane trafficking. Annu. Rev Biochem. 1994, 63 63-100. 

Typically, the presynaptic ending is further distinguished from the postsynaptic component by the conspicuous presence of neurotransmitter-filled vesicles. In response to presynaptic membrane depolarization, the vesicles exocytose their contents into the cleft through complicated membrane-trafficking events. The presynaptic axon terminal (bouton) of the presynaptic component also contains other organelles such as mitochondria, smooth endoplasmic reticulum, microtubules, and neurofilaments. The presynaptic membrane is variably populated by docking/fusion apparatus, ion channels, and other protein constituents. The 20-30 nM wide synaptic cleft separates the pre- and postsynaptic membranes and generally contains a dense plaque of intercellular material that includes microfilaments. 

Type III coronins are different from other coronins in that they consist of two coronins fused in tandem but lacking coiled-coiled domains. In humans, they are represented by coronin 7. Type III coronins from Caenorhabditis (POD-1) sxiA Drosophila (Dpodl) have been shown to be involved with actin but seem participate in different processes. The embryonic-lethal phenotype of POD-1 mutants suggests that it is required for polarized membrane trafficking necessary for the establishment of anterior-posterior polarity in the embryo. Consistent with this phenotype, coronin 7 is associated with the Golgi apparatus and has been impheated in vesicle trafficking ... 

The observed phenotypes of the coro mutants were also remarkably similar to phenotypes reported for syntaxinlA syxlA) alleles. SyxlA, a member of the SNARE complex, is required for membrane trafficking associated with synaptic vesicles or other small vesicles such as endosomes. Based on their observations the authors concluded that D. melanogaster coro protein functions with syxlA to mediate trafficking and fusion of F-actin coated vesicles with the membrane. It appears that coro displays the same biological functions like thcD. discoideum coroiun. In addition, the results on cloning and characterization of coro provide new ins hts into the role of the actin cytoskeleton in various developmental processes. 

Kinesin participates in vesicle transport in a number of cell types, including fast axonal transport in neurons (56). In Sertoli cells, kinesin has been observed to localize to the trans Golgi network, a location suggesting involvement in membrane trafficking within the cell (57). In addition, kinesin is localized to ectoplasmic specializations where it may be involved in the movement and positioning of elongate spermatids within the seminiferous epithelium (55). 

Sec 18 is a yeast gene that encodes NSF. It is a class C mutant in the yeast secretory pathway. What is the mechanistic role of NSF in membrane trafficking. As indicated by its class C phenotype, why does an NSF mutation produce accumulation of vesicles at what appears to be only one stage of the secretory pathway ... 

Several types of evidence suggest that myosin V also participates In the Intracellular transport of membrane-bounded vesicles. For example, mutations In the myosin V gene In yeast disrupt protein secretion and lead to an accumulation of vesicles In the c rt oplasm. Vertebrate brain tissue Is rich In myosin V, which Is concentrated on Golgi stacks. This association with membranes Is consistent with the effects of myosin V mutations In mice. Such mutations are associated with defects In synaptic transmission and eventually cause death from seizures. Myosin VI also Is Implicated In membrane trafficking of vesicles. 

Dynein seems to be a complementary partner of kInesIn and myosin In trafficking vesicles and chromosomes. Although an emerging theme Is that dynactin couples a membrane cargo to dynein or kinesin, how microtubule-based movements are coordinated with myosin-based movements remains an unresolved question. Several lines of Investigation suggest that dynein could play a central role In coordination. Because the (+) ends of actin filaments and microtubules tend to point toward the cell periphery, dynein Is the only major class of motors that moves toward the cell Interior. The location of cytoplasmic dynein In the actin-rich cortex Is similar to that of myosin and distinct from that of kinesin. Whether dynactin also couples myosin to membrane trafficking Is unknown. 

Thus, CI-976 affects multiple membrane trafficking pathways, suggesting a role for LPATs at several distinct steps in both membrane vesicle and tubule formation. This article describes the general properties of CI-976,... 

The formation of vesicles or trafficking intermediates is a complex process, requiring interplay between numerous soluble and membrane-bound proteins and lipids. Together these components work to generate local deformation of a membrane, capture cargo, and promote the formation of a vesicle or tubule intermediate. In cells, these processes can be examined by deleting individual components or by over-expressing... 

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