Regulation of Notch signalling by non-visual beta-arrestin

Nat Cell Biol. 2005 Dec;7(12):1191-201. doi: 10.1038/ncb1327. Epub 2005 Nov 13.

Abstract

Signalling activity of the Notch receptor, which plays a fundamental role in metazoan cell fate determination, is controlled at multiple levels. We uncovered a Notch signal-controlling mechanism that depends on the ability of the non-visual beta-arrestin, Kurtz (Krz), to influence the degradation and, consequently, the function of the Notch receptor. We identified Krz as a binding partner of a known Notch-pathway modulator, Deltex (Dx), and demonstrated the existence of a trimeric Notch-Dx-Krz protein complex. This complex mediates the degradation of the Notch receptor through a ubiquitination-dependent pathway. Our results establish a novel mode of regulation of Notch signalling and define a new function for non-visual beta-arrestins.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arrestins / genetics
  • Arrestins / metabolism
  • Arrestins / physiology*
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Drosophila Proteins / physiology
  • Female
  • Male
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Multiprotein Complexes
  • Mutation / physiology
  • Receptors, Notch / metabolism*
  • Signal Transduction*
  • Two-Hybrid System Techniques
  • Ubiquitin / metabolism
  • Wings, Animal / growth & development
  • beta-Arrestins

Substances

  • Arrestins
  • DX protein, Drosophila
  • Drosophila Proteins
  • Membrane Proteins
  • Multiprotein Complexes
  • N protein, Drosophila
  • Receptors, Notch
  • Ubiquitin
  • beta-Arrestins
  • krz protein, Drosophila