vesicular transport
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The compartments of the secretory and endocytic pathways are in constant communication with one another and this is thought to occur through vesicular (or in some cases tubular) transport intermediates. A typical vesicular transport step can be viewed as a four-stage process.
Cellular organelles in the exocytic pathway and endocytic pathway have a distinctive spatial distribution. They communicate through an elaborate system of vesiculo-tubular transport (vesicular transport or vesicle transport).
Proteins and lipids to be transported are sorted to specific sites on the donor membrane, or compartment, and transport vesicles bud with the aid of cytosolic complexes of coat proteins.
Vesicles move along cytoskeletal tracks, either microtubules or actin filaments, with the help of motor proteins.
The vesicle is tethered and docked near the target membrane and subsequently fuses with the acceptor bilayer, releasing its contents into the target, or acceptor, compartment.
Vesicular coat proteins mediate the formation of nascent vesicles and select the cargo to be incorporated therein.
As additional coat proteins are discovered that regulate vesicular traffic along very specific intracellular pathways, the possibility looms of regulating the intracellular trafficking and targeting of therapeutic agents by modulation of the action of vesicular coat proteins.
Examples are provided of coat proteins thought to regulate the trafficking of pharmaceutically relevant molecules via clathrin-mediated endocytosis, caveolae-mediated endocytosis, and transcytosis.
Vesicular transport steps
Step 1: In the first stage, cargo molecules are concentrated in a region of the donor compartment and are enclosed in a budding vesicle, which then detaches from the donor organelle membrane. Several Rabs such as RAB1, RAB2, RAB5 and RAB9 have been implicated in this process.
Step 2: The vesicle moves through the cytoplasm along cytoskeletal filaments such as microtubules (MT) and/or actin. Several Rabs such as Sec4, Rab5 (RAB5), Rab6 (RAB6) and Rab27 (RAB27A and RAB27B) have been implicated in this process.
Step 3: The vesicle then forms a close physical association with target membrane referred to as docking/tethering. Several Rabs such as Ypt1, Ypt7, Sec4, Rab1 (RAB1) and Rab5 (RAB5) have been implicated in this process.
STep 4: Finally, membrane fusion between the transport vesicle and an acceptor compartment proceeds resulting in release of vesicle contents into the lumen of the target organelle (or extracellular space).
NB: Each Rab functions in a specific step within a pathway, such as ER-Golgi transport for Ypt1 and Rab1, but that some RABs function in several consecutive stages of the same transport step, such as Rab5 (RAB5) involved in stages 1, 2 and 3 in plasma membrane-early endosome transport.
Members
Pathology: dysfunctions of vesicular-transport mechanisms
genetic dysfunctions of vesicular transport
infectious diseases
- Several microbial pathogens are capable of escaping immune surveillance by interfering with host-cell antigen presentation.
- This can be accomplished by disturbing the intracellular sorting of multiple histocompatibility complex proteins, which then become unable to reach the surface of the cell.
See also
protein transport
- vesicle-mediated protein transport
References
Olkkonen VM, Ikonen E. Genetic defects of intracellular-membrane transport. N Engl J Med. 2000 Oct 12;343(15):1095-104. PMID: 11027745