Membrane Traffic and Disease


Membrane traffic is a highly regulated process that ensures the communication between membrane‐bound compartments while maintaining their specific protein and lipid composition. It can be divided into four steps: cargo sorting and budding of a vesicle from a donor compartment, transport along the cytoskeleton, tethering and docking to an acceptor compartment, and finally fusion with the acceptor compartment. Importantly, defects in any of these steps can lead to diseases that affect different tissues and organs. At the subcellular level, several of these diseases affect compartments from specialized cell types known as lysosome‐related organelles. Moreover, the dysfunction of membrane traffic processes required ubiquitously can lead to restricted phenotypes, underscoring the redundancy of these processes and/or the sensitivity of certain cell types to their impairment. Thus, the study of the diseases caused by defects in membrane traffic provides an opportunity to understand its role in normal cell physiology and discover novel therapies.

Key Concepts:

  • Defects in any of the steps of vesicular traffic can lead to disease.

  • Vesicular traffic regulation shows redundancy.

  • Defects in ubiquitously‐expressed proteins can result in a tissue‐restricted phenotype.

  • Lysosome‐related organelles are commonly affected upon impairment of vesicular traffic.

  • Several diseases are caused by defects in different proteins involved in the same biological process/pathway.

Keywords: vesicular traffic; Rab; Arf; SNARE ; coat protein; kinesin; myosin; dynein; small G protein; lysosome‐related organelle

Figure 1.

Membrane traffic steps and diseases caused by their impairment. Nascent‐coated vesicles bud from donor compartments and are transported along the cytoskeleton via molecular motor proteins. Vesicles are tethered and docked to the acceptor compartments before SNARE‐mediated fusion with the latter. Diseases that are caused by dysfunction of these steps are indicated. CEDNIK – Cerebral dysgenesis, neuropathy, ichthyosis, and keratoderma syndrome; CLSD – Cranio‐lenticulo‐sutural dysplasia; CMRD – Chylomicron retention disease; CMT – Charcot‐Marie‐Tooth type 2; FHL – Familial hemophagocytic lymphohistiocytosis; GS – Griscelli syndrome; HPS – Hermansky‐Pudlak syndrome; KS – Kartagener syndrome (Primary ciliary dyskinesia); MVID – Microvillus inclusion disease; SEDT – Spondyloepiphyseal dysplasia tarda; SPG10 – Spastic paraplegia type 10; USH1B – Usher syndrome type 1B.



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Further Reading

Aridor M and Hannan LA (2000) Traffic jam: a compendium of human diseases that affect intracellular transport processes. Traffic (Copenhagen, Denmark) 1: 836–851.

Aridor M and Hannan LA (2002) Traffic jams II: an update of diseases of intracellular transport. Traffic (Copenhagen, Denmark) 3: 781–790.

Bucci C , Bakke O and Progida C (2012) Charcot‐Marie‐Tooth disease and intracellular traffic. Progress in Neurobiology 99: 191–225.

Garcia‐Gonzalo FR and Reiter JF (2012) Scoring a backstage pass: mechanisms of ciliogenesis and ciliary access. Journal of Cell Biology 197: 697–709.

Gentil BJ and Cooper L (2012) Molecular basis of axonal dysfunction and traffic impairments in CMT. Brain Research Bulletin 88: 444–453.

Howell GJ , Holloway ZG , Cobbold C , Monaco AP and Ponnambalam S (2006) Cell biology of membrane trafficking in human disease. International Review of Cytology 252: 1–69.

Hutagalung AH and Novick PJ (2011) Role of Rab GTPases in membrane traffic and cell physiology. Physiological Reviews 91: 119–149.

Krzewski K and Cullinane AR (2013) Evidence for defective Rab GTPase‐dependent cargo traffic in immune disorders. Experimental Cell Research 319: 2360–2367.

Olkkonen VM and Ikonen E (2006) When intracellular logistics fails – genetic defects in membrane trafficking. Journal of Cell Science 119: 5031–5045.

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Cláudio, Nuno, Pereira, Francisco JC, and Barral, Duarte C(Nov 2014) Membrane Traffic and Disease. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0020892]