TY - JOUR
T1 - Ligand-independent traffic of notch buffers activated armadillo in Drosophila
AU - Sanders, Phil G. T.
AU - Muñoz-Descalzo, Silvia
AU - Balayo, Tina
AU - Wirtz-Peitz, Frederik
AU - Hayward, Penelope
AU - Martinez Arias, Alfonso
PY - 2009/8/11
Y1 - 2009/8/11
N2 - Notch receptors act as ligand-dependent membrane-tethered transcription factors with a prominent role in binary cell fate decisions during development, which is conserved across species. In addition there is increasing evidence for other functions of Notch, particularly in connection with Wnt signalling: Notch is able to modulate the activity of Armadillo/ßcatenin, the effector of Wnt signalling, in a manner that is independent of its transcriptional activity. Here we explore the mechanism of this interaction in the epithelium of the Drosophila imaginal discs and find that it is mediated by the ligand-independent endocytosis and traffic of the Notch receptor. Our results show that Notch associates with Armadillo near the adherens junctions and that it is rapidly endocytosed promoting the traffic of an activated form of Armadillo into endosomal compartments, where it may be degraded. As Notch has the ability to interact with and downregulate activated forms of Armadillo, it is possible that in vivo Notch regulates the transcriptionally competent pool of Armadillo. These interactions reveal a previously unknown activity of Notch, which serves to buffer the function of activated Armadillo and might underlie some of its transcription-independent effects.
AB - Notch receptors act as ligand-dependent membrane-tethered transcription factors with a prominent role in binary cell fate decisions during development, which is conserved across species. In addition there is increasing evidence for other functions of Notch, particularly in connection with Wnt signalling: Notch is able to modulate the activity of Armadillo/ßcatenin, the effector of Wnt signalling, in a manner that is independent of its transcriptional activity. Here we explore the mechanism of this interaction in the epithelium of the Drosophila imaginal discs and find that it is mediated by the ligand-independent endocytosis and traffic of the Notch receptor. Our results show that Notch associates with Armadillo near the adherens junctions and that it is rapidly endocytosed promoting the traffic of an activated form of Armadillo into endosomal compartments, where it may be degraded. As Notch has the ability to interact with and downregulate activated forms of Armadillo, it is possible that in vivo Notch regulates the transcriptionally competent pool of Armadillo. These interactions reveal a previously unknown activity of Notch, which serves to buffer the function of activated Armadillo and might underlie some of its transcription-independent effects.
UR - http://www.scopus.com/inward/record.url?scp=69349094389&partnerID=8YFLogxK
UR - http://dx.doi.org//10.1371/journal.pbio.1000169
U2 - 10.1371/journal.pbio.1000169
DO - 10.1371/journal.pbio.1000169
M3 - Article
AN - SCOPUS:69349094389
SN - 1544-9173
VL - 7
JO - PLoS Biology
JF - PLoS Biology
IS - 8
M1 - e1000169
ER -