vesicle trafficking

Vesicular transport of proteins is carried out by the formation of coated vesicles from a donor compartment, followed by their uncoating and subsequent docking and fusion of the vesicles with a target compartment membrane.

The major cellular routes of membrane transport are the biosynthetic pathway responsible for the transport of proteins synthesized in the endoplasmic reticulum to the extracellular space (secretion) or to other cellular-membrane compartments and the endocytic pathway responsible for the uptake of compounds from the extracellular milieu to be used in cellular metabolism.

Most membrane and secretory proteins, as well as many lipids, are synthesized in the endoplasmic reticulum, whose luminal environment is especially suited to facilitate the proper folding of the synthesized proteins and the initial steps of the glycosylation of proteins.

Proteins that are destined to be transported out of the endoplasmic reticulum move on to the Golgi apparatus, where further post-translational modifications occur.

Subsequently, the proteins are sorted according to their destinations: the plasma membrane (e.g., ion channels, adhesion molecules, and various receptors), regulated secretory granules or vesicles (e.g., hormones, enzymes, and neurotransmitters), or organelles of the endocytic pathway (e.g., lysosomal hydrolases).

Defects in Intracellular Protein Transport

 Defects Affecting the Protein-Sorting Apparatus

• inclusion-cell disease (mucolipidosis II)

• defect in the coat-protein complexes
  • Hermansky-Pudlak syndrome
  • Chédiak-Higashi syndrome

 Defects in Cytoskeletal Proteins Involved in Membrane Transport

• Griscelli’s syndrome (RAB27A and MYO5 mutations)
• Elejalde’s syndrome (MYO5 mutations)

 Defects in the Machinery for the Docking and Fusion of Transport Vesicles

• mutations in the auxiliary protein factors controlling the membrane association of the Rab GTPases
  • choroideremia
  • X-linked nonspecific mental retardation

 Lipid Disorders Affecting Vesicular Transport

• oculocerebrorenal syndrome

Features

 endosomal/trans-Golgi transportation vesicles
 SNARE complex
 monoubiquitin (monoUb)

Animations

 Axonal transport: A movie from J Cell Biol

References

 Toonen RF, Verhage M. Vesicle trafficking: pleasure and pain from SM genes. Trends Cell Biol. 2003 Apr;13(4):177-86. PMID: 12667755

 Karcher RL, Deacon SW, Gelfand VI. Motor-cargo interactions : the key to transport specificity. Trends Cell Biol. 2002 Jan ;12(1):21-7. PMID : 11854006

 Guo W, Sacher M, Barrowman J, Ferro-Novick S, Novick P. Protein complexes in transport vesicle targeting. Trends Cell Biol. 2000 Jun;10(6):251-5. PMID: 10802541

 Olkkonen VM, Ikonen E. Genetic defects of intracellular-membrane transport. N Engl J Med. 2000 Oct 12;343(15):1095-104. PMID: 11027745

 Spritz RA. Multi-organellar disorders of pigmentation: intracellular traffic jams in mammals, flies and yeast. Trends Genet. 1999 Sep;15(9):337-40. PMID: 10461199