Secreted Wingless-interacting molecule (Swim) promotes long-range signaling by maintaining Wingless solubility

被引:136
作者
Mulligan, Kimberly A. [1 ]
Fuerer, Christophe [2 ]
Ching, Wendy [2 ]
Fish, Matt [2 ]
Willert, Karl [2 ]
Nusse, Roeland [1 ,2 ]
机构
[1] Stanford Univ, Howard Hughes Med Inst, Sch Med, Stanford, CA 94305 USA
[2] Stanford Univ, Dept Dev Biol, Sch Med, Stanford, CA 94305 USA
基金
美国国家卫生研究院; 瑞士国家科学基金会;
关键词
development; morphogenesis; pattern; palmitoylation; lipid modification; LIPOCALIN PROTEIN FAMILY; MORPHOGEN GRADIENT; WNT PROTEIN; DROSOPHILA; HEDGEHOG; CELLS; RECEPTOR; PATHWAY; GROWTH; PALMITOYLATION;
D O I
10.1073/pnas.1119197109
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Lipid-modified Wnt/Wingless (Wg) proteins can signal to their target cells in a short-or long-range manner. How these hydrophobic proteins travel through the extracellular environment remains an outstanding question. Here, we report on a Wg binding protein, Secreted Wg-interacting molecule (Swim), that facilitates Wg diffusion through the extracellular matrix. Swim, a putative member of the Lipocalin family of extracellular transport proteins, binds to Wg with nanomolar affinity in a lipid-dependent manner. In quantitative signaling assays, Swim is sufficient to maintain the solubility and activity of purified Wg. In Drosophila, swim RNAi phenotypes resemble wg loss-of-function phenotypes in long-range signaling. We propose that Swim is a cofactor that promotes long-range Wg signaling in vivo by maintaining the solubility of Wg.
引用
收藏
页码:370 / 377
页数:8
相关论文
共 48 条
[1]   Wingless Promotes Proliferative Growth in a Gradient-Independent Manner [J].
Baena-Lopez, Luis Alberto ;
Franch-Marro, Xavier ;
Vincent, Jean-Paul .
SCIENCE SIGNALING, 2009, 2 (91) :ra60
[2]   A new member of the frizzled family from Drosophila functions as a Wingless receptor [J].
Bhanot, P ;
Brink, M ;
Samos, CH ;
Hsieh, JC ;
Wang, YS ;
Macke, JP ;
Andrew, D ;
Nathans, J ;
Nusse, R .
NATURE, 1996, 382 (6588) :225-230
[3]   Wingless repression of Drosophila frizzled 2 expression shapes the wingless morphogen gradient in the wing [J].
Cadigan, KM ;
Fish, MP ;
Rulifson, EJ ;
Nusse, R .
CELL, 1998, 93 (05) :767-777
[4]   Lipid-independent secretion of a Drosophila Wnt protein [J].
Ching, Wendy ;
Hang, Howard C. ;
Nusse, Roel .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2008, 283 (25) :17092-17098
[5]   Wnt/β-catenin signaling in development and disease [J].
Clevers, Hans .
CELL, 2006, 127 (03) :469-480
[6]  
Day SJ, 2000, DEVELOPMENT, V127, P2977
[7]  
Flower DR, 1996, BIOCHEM J, V318, P1
[8]   The lipocalin protein family: structural and sequence overview [J].
Flower, DR ;
North, ACT ;
Sansom, CE .
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEIN STRUCTURE AND MOLECULAR ENZYMOLOGY, 2000, 1482 (1-2) :9-24
[9]   Glypicans shunt the Wingless signal between local signalling and further transport [J].
Franch-Marro, X ;
Marchand, O ;
Piddini, E ;
Ricardo, S ;
Alexandre, C ;
Vincent, JP .
DEVELOPMENT, 2005, 132 (04) :659-666
[10]   Wingless secretion requires endosome-to-Golgi retrieval of Wntless/Evi/Sprinter by the retromer complex [J].
Franch-Marro, Xavier ;
Wendler, Franz ;
Guidato, Sonia ;
Griffith, Janice ;
Baena-Lopez, Alberto ;
Itasaki, Nobue ;
Maurice, Madelon M. ;
Vincent, Jean-Paul .
NATURE CELL BIOLOGY, 2008, 10 (02) :170-U40