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：

瑞士国家科学基金会; 美国国家卫生研究院;

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

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