Furin cleavage is not a requirement for Drosophila Notch function.
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.
Kidd
Simon
S
Laboratory of Genetics, The Rockefeller University, New York, NY 10021, USA. kidd@mail.rockefeller.edu
Lieber
Toby
T
D000595:Amino Acid Sequence; D000818:Animals; D051186:Armadillo Domain Proteins; D001921:Brain / Q000196:embryology / Q000378:metabolism; D029721:Drosophila Proteins / Q000378:metabolism; D004331:Drosophila melanogaster / Q000196:embryology / Q000378:metabolism; D045683:Furin; D006023:Glycoproteins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D008969:Molecular Sequence Data; D051880:Receptors, Notch; D012097:Repressor Proteins / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013381:Subtilisins / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors
C495305:ARM protein, Drosophila; D051186:Armadillo Domain Proteins; D029721:Drosophila Proteins; D006023:Glycoproteins; D008565:Membrane Proteins; C497759:N protein, Drosophila; D051880:Receptors, Notch; D012097:Repressor Proteins; C088731:Su(H) protein, Drosophila; D015534:Trans-Activators; D014157:Transcription Factors; C066579:sca protein, Drosophila; D013381:Subtilisins; D045683:Furin