Membrane trafficking of death receptors: implications on signalling

Int J Mol Sci. 2013 Jul 11;14(7):14475-503. doi: 10.3390/ijms140714475.

Abstract

Death receptors were initially recognised as potent inducers of apoptotic cell death and soon ambitious attempts were made to exploit selective ignition of controlled cellular suicide as therapeutic strategy in malignant diseases. However, the complexity of death receptor signalling has increased substantially during recent years. Beyond activation of the apoptotic cascade, involvement in a variety of cellular processes including inflammation, proliferation and immune response was recognised. Mechanistically, these findings raised the question how multipurpose receptors can ensure selective activation of a particular pathway. A growing body of evidence points to an elegant spatiotemporal regulation of composition and assembly of the receptor-associated signalling complex. Upon ligand binding, receptor recruitment in specialized membrane compartments, formation of receptor-ligand clusters and internalisation processes constitute key regulatory elements. In this review, we will summarise the current concepts of death receptor trafficking and its implications on receptor-associated signalling events.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Apoptosis
  • Fas Ligand Protein / metabolism
  • Humans
  • Receptors, Death Domain / chemistry
  • Receptors, Death Domain / metabolism*
  • Receptors, TNF-Related Apoptosis-Inducing Ligand / metabolism
  • Receptors, Tumor Necrosis Factor / metabolism
  • Signal Transduction
  • TNF-Related Apoptosis-Inducing Ligand / metabolism
  • Tumor Necrosis Factors / metabolism
  • fas Receptor / metabolism

Substances

  • Fas Ligand Protein
  • Receptors, Death Domain
  • Receptors, TNF-Related Apoptosis-Inducing Ligand
  • Receptors, Tumor Necrosis Factor
  • TNF-Related Apoptosis-Inducing Ligand
  • Tumor Necrosis Factors
  • fas Receptor