Furin cleavage is not a requirement for Drosophila Notch function

Mech Dev. 2002 Jul;115(1-2):41-51. doi: 10.1016/s0925-4773(02)00120-x.

Abstract

Notch (N) is a large transmembrane protein that acts as a receptor in an evolutionarily conserved intercellular signalling pathway. Because of this conservation, it has been assumed that biochemical events mediating N function are identical in all species. For instance, intracellular maturation by furin protease and subunit assembly leading to the formation of a heterodimeric cell surface N receptor are thought to be central to its function in both mammals and flies. However, in Drosophila the majority of N appears to be full-length. It has not been determined whether this full-length N protein is on the cell surface. We describe experiments which indicate that unlike mammalian N, the majority of Drosophila N on the cell surface is full-length and that in Drosophila, in vivo, furin cleavage is not required for biological activity. We further show that the behaviour of fly and mouse N can be interchanged simply by swapping the regions in which the mammalian furin-like cleavage site is located.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Armadillo Domain Proteins
  • Brain / embryology
  • Brain / metabolism
  • Drosophila Proteins / metabolism
  • Drosophila melanogaster / embryology
  • Drosophila melanogaster / metabolism
  • Furin
  • Glycoproteins / metabolism
  • Membrane Proteins / metabolism*
  • Molecular Sequence Data
  • Receptors, Notch
  • Repressor Proteins / metabolism
  • Sequence Homology, Amino Acid
  • Subtilisins / metabolism*
  • Trans-Activators / metabolism
  • Transcription Factors

Substances

  • ARM protein, Drosophila
  • Armadillo Domain Proteins
  • Drosophila Proteins
  • Glycoproteins
  • Membrane Proteins
  • N protein, Drosophila
  • Receptors, Notch
  • Repressor Proteins
  • Su(H) protein, Drosophila
  • Trans-Activators
  • Transcription Factors
  • sca protein, Drosophila
  • Subtilisins
  • Furin