Pentagone internalises glypicans to fine-tune multiple signalling pathways.
Tight regulation of signalling activity is crucial for proper tissue patterning and growth. Here we investigate the function of Pentagone (Pent), a secreted protein that acts in a regulatory feedback during establishment and maintenance of BMP/Dpp morphogen signalling during Drosophila wing development. We show that Pent internalises the Dpp co-receptors, the glypicans Dally and Dally-like protein (Dlp), and propose that this internalisation is important in the establishment of a long range Dpp gradient. Pent-induced endocytosis and degradation of glypicans requires dynamin- and Rab5, but not clathrin or active BMP signalling. Thus, Pent modifies the ability of cells to trap and transduce BMP by fine-tuning the levels of the BMP reception system at the plasma membrane. In addition, and in accordance with the role of glypicans in multiple signalling pathways, we establish a requirement of Pent for Wg signalling. Our data propose a novel mechanism by which morphogen signalling is regulated.
Centre for Biological Signalling Studies, Albert-Ludwigs-University of Freiburg, Breisgau, Germany.
Mark
M
Norman
Institute for Biology I, Albert-Ludwigs-University of Freiburg, Breisgau, Germany.
Robin
R
Vuilleumier
Institute for Biology I, Albert-Ludwigs-University of Freiburg, Breisgau, Germany.|Spemann Graduate School of Biology and Medicine, Albert-Ludwigs-University of Freiburg, Breisgau, Germany.
Alexander
A
Springhorn
Centre for Biological Signalling Studies, Albert-Ludwigs-University of Freiburg, Breisgau, Germany.|Spemann Graduate School of Biology and Medicine, Albert-Ludwigs-University of Freiburg, Breisgau, Germany.
Jennifer
J
Gawlik
Centre for Biological Signalling Studies, Albert-Ludwigs-University of Freiburg, Breisgau, Germany.|Institute for Biology I, Albert-Ludwigs-University of Freiburg, Breisgau, Germany.
George
0000-0002-2142-5943
G
Pyrowolakis
D000818:Animals; D004330:Drosophila / Q000196:embryology*; D029721:Drosophila Proteins / Q000378:metabolism*; D034281:Dynamins / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D011509:Proteoglycans / Q000378:metabolism*; D015398:Signal Transduction; D014921:Wings, Animal / Q000196:embryology*; D020696:rab5 GTP-Binding Proteins / Q000378:metabolism
D029721:Drosophila Proteins; D016326:Extracellular Matrix Proteins; C562078:Magu protein, Drosophila; D011509:Proteoglycans; C420997:dlp protein, Drosophila; C064196:dpp protein, Drosophila; D020696:rab5 GTP-Binding Proteins; D034281:Dynamins
D. melanogaster; cell biology; decapentaplegic; developmental biology; endocytosis; glypicans; morphogen; stem cells