Dally and Notum regulate the switch between low and high level Hedgehog pathway signalling

被引:18
作者
Ayers, Katie L. [2 ]
Mteirek, Rana [3 ]
Cervantes, Alexandra [4 ]
Lavenant-Staccini, Laurence [1 ]
Therond, Pascal P. [1 ]
Gallet, Armel [5 ]
机构
[1] Univ Nice Sophia Antipolis, Inst Biol Valrose, UMR CNRS 7277, UMR Inserm 1091, F-06108 Nice 02, France
[2] Royal Childrens Hosp, Murdoch Childrens Res Inst, Parkville, Vic 3052, Australia
[3] Univ Clermont Ferrand, INSERM, Lab GReD UMR6247, Fac Med,CNRS U931, F-63001 Clermont Ferrand, France
[4] VIRBAC, F-06517 Carros, France
[5] Univ Nice, CNRS 7254, UMR INRA 1355, Inst Sophia Agrobiotech, F-06903 Sophia Antipolis, France
来源
DEVELOPMENT | 2012年 / 139卷 / 17期
关键词
Hedgehog; Morphogen; Proteoglycans; Drosophila; INTEGRAL MEMBRANE PROTEOGLYCAN; HEPARAN-SULFATE INTERACTIONS; WINGLESS MORPHOGEN GRADIENT; LONG-RANGE ACTIVITY; CELL-SURFACE; CHOLESTEROL MODIFICATION; GOLGI ORGANIZATION; DROSOPHILA; IHOG; GLYPICANS;
D O I
10.1242/dev.078402
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
During development, secreted morphogens, such as Hedgehog (Hh), control cell fate and proliferation. Precise sensing of morphogen levels and dynamic cellular responses are required for morphogen-directed morphogenesis, yet the molecular mechanisms responsible are poorly understood. Several recent studies have suggested the involvement of a multi-protein Hh reception complex, and have hinted at an understated complexity in Hh sensing at the cell surface. We show here that the expression of the proteoglycan Dally in Hh-receiving cells in Drosophila is necessary for high but not low level pathway activity, independent of its requirement in Hh-producing cells. We demonstrate that Dally is necessary to sequester Hh at the cell surface and to promote Hh internalisation with its receptor. This internalisation depends on both the activity of the hydrolase Notum and the glycosyl-phosphatidyl-inositol (GPI) moiety of Dally, and indicates a departure from the role of the second glypican Dally-like in Hh signalling. Our data suggest that hydrolysis of the Dally-GPI by Notum provides a switch from low to high level signalling by promoting internalisation of the Hh-Patched ligand-receptor complex.
引用
收藏
页码:3168 / 3179
页数:12
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