Balanced ubiquitination determines cellular responsiveness to extracellular stimuli

Cell Mol Life Sci. 2012 Dec;69(23):4007-16. doi: 10.1007/s00018-012-1084-4. Epub 2012 Jul 24.

Abstract

Signal strength evoked by ligand stimulation is crucial for cellular responses such as fate decision, cell survival/death, secretion, and migration. For example, morphogens are secreted signaling molecules that form concentration gradients within tissues and induce distinct cell fates in a signal strength-dependent manner. In addition to extracellular ligand abundance, the sensitivity of signal-receiving cells to ligands also influences signal strength. Cell sensitivity to ligands is controlled at various levels: receptor presentation at the cell surface, positive/negative regulation of signal transduction, and target gene activation/repression. While the regulation of signal transduction and gene transcription is well studied, receptor presentation is still not fully understood. Recently, it was reported that cellular sensitivity to the Wingless (Wg)/Wnt morphogen is regulated by balanced ubiquitination and deubiquitination of its receptor Frizzled (Fz). In this review, we review how ubiquitination regulates receptor presentation at the cell surface for the detection of extracellular signal strength.

Publication types

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

MeSH terms

  • Animals
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / metabolism
  • Endosomes / metabolism
  • Frizzled Receptors / metabolism*
  • Lysosomes / metabolism
  • Models, Biological
  • Signal Transduction*
  • Ubiquitination*
  • rab GTP-Binding Proteins / metabolism

Substances

  • Drosophila Proteins
  • Frizzled Receptors
  • rab GTP-Binding Proteins