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

Proc Natl Acad Sci U S A. 2012 Jan 10;109(2):370-7. doi: 10.1073/pnas.1119197109. Epub 2011 Dec 27.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Biological Transport / physiology
  • DNA Primers / genetics
  • Drosophila / genetics
  • Drosophila / metabolism*
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Enzyme-Linked Immunosorbent Assay
  • Extracellular Matrix / metabolism
  • Immunohistochemistry
  • Lipocalins / genetics
  • Lipocalins / metabolism*
  • Molecular Sequence Data
  • Plasmids / genetics
  • RNA Interference
  • Real-Time Polymerase Chain Reaction
  • Sequence Alignment
  • Signal Transduction / genetics
  • Signal Transduction / physiology*
  • Solubility
  • Wnt1 Protein / metabolism*

Substances

  • DNA Primers
  • Drosophila Proteins
  • Lipocalins
  • Swim protein, Drosophila
  • Wnt1 Protein
  • wg protein, Drosophila