Secreted Wingless-interacting molecule (Swim) promotes long-range signaling by maintaining Wingless solubility.
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.
The Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.
Kimberly A
KA
Mulligan
Christophe
C
Fuerer
Wendy
W
Ching
Matt
M
Fish
Karl
K
Willert
Roeland
R
Nusse
D000595:Amino Acid Sequence; D000818:Animals; D001692:Biological Transport / Q000502:physiology; D017931:DNA Primers / Q000235:genetics; D004330:Drosophila / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005109:Extracellular Matrix / Q000378:metabolism; D007150:Immunohistochemistry; D054834:Lipocalins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D010957:Plasmids / Q000235:genetics; D034622:RNA Interference; D060888:Real-Time Polymerase Chain Reaction; D016415:Sequence Alignment; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D012995:Solubility; D051155:Wnt1 Protein / Q000378:metabolism*
D017931:DNA Primers; D029721:Drosophila Proteins; D054834:Lipocalins; C570447:Swim protein, Drosophila; D051155:Wnt1 Protein; C074622:wg protein, Drosophila