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

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2012年 / 109卷 / 02期

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

页码：370 / 377

页数：8

共 48 条

[41] TIN-ag-RP, a novel catalytically inactive cathepsin B-related protein with EGF domains, is predominantly expressed in vascular smooth muscle cells [J].

Wex, T ;

Lipyansky, A ;

Brömme, NC ;

Wex, H ;

Guan, XQ ;

Brömme, D .

BIOCHEMISTRY, 2001, 40 (05) :1350-1357

[42] Wnt proteins are lipid-modified and can act as stem cell growth factors [J].

Willert, K ;

Brown, JD ;

Danenberg, E ;

Duncan, AW ;

Weissman, IL ;

Reya, T ;

Yates, JR ;

Nusse, R .

NATURE, 2003, 423 (6938) :448-452

[43] Ligand receptor interactions in the Wnt signaling pathway in Drosophila [J].

Wu, CH ;

Nusse, R .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (44) :41762-41769

[44] β-lactoglobulin binds palmitate within its central cavity [J].

Wu, SY ;

Pèrez, MD ;

Puyol, P ;

Sawyer, L .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (01) :170-174

[45] Direct and long-range action of a wingless morphogen gradient [J].

Zecca, M ;

Basler, K ;

Struhl, G .

CELL, 1996, 87 (05) :833-844

[46]

ZECCA M, 1995, DEVELOPMENT, V121, P2265

[47] A Feed-Forward Circuit Linking Wingless, Fat-Dachsous Signaling, and the Warts-Hippo Pathway to Drosophila Wing Growth [J].

Zecca, Myriam ;

Struhl, Gary .

PLOS BIOLOGY, 2010, 8 (06)

[48] Drosophila Wnt-1 undergoes a hydrophobic modification and is targeted to lipid rafts, a process that requires porcupine [J].

Zhai, L ;

Chaturvedi, D ;

Cumberledge, S .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (32) :33220-33227

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