Abstract
A relatively small number of proteins have been suggested to act as morphogens-signalling molecules that spread within tissues to organize tissue repair and the specification of cell fate during development. Among them are Wnt proteins, which carry a palmitoleate moiety that is essential for signalling activity1-3. How a hydrophobic lipoprotein can spread in the aqueous extracellular space is unknown. Several mechanisms, such as those involving lipoprotein particles, exosomes or a specific chaperone, have been proposed to overcome this so-called Wnt solubility problem4-6. Here we provide evidence against these models and show that the Wnt lipid is shielded by the core domain of a subclass of glypicans defined by the Dally-like protein (Dlp). Structural analysis shows that, in the presence of palmitoleoylated peptides, these glypicans change conformation to create a hydrophobic space. Thus, glypicans of the Dlp family protect the lipid of Wnt proteins from the aqueous environment and serve as a reservoir from which Wnt proteins can be handed over to signalling receptors.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing / chemistry
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Adaptor Proteins, Signal Transducing / genetics
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Adaptor Proteins, Signal Transducing / metabolism
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Animals
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Cell Cycle Proteins / chemistry
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Cell Cycle Proteins / metabolism
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Drosophila Proteins / chemistry
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Drosophila Proteins / metabolism
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Drosophila melanogaster
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Fatty Acids, Monounsaturated / chemistry
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Fatty Acids, Monounsaturated / metabolism
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Female
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Glypicans / chemistry*
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Glypicans / classification
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Glypicans / metabolism*
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Humans
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Hydrophobic and Hydrophilic Interactions
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Lipids* / chemistry
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Male
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Models, Molecular
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Mutation
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Nuclear Proteins / chemistry
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism
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Protein Binding / genetics
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Protein Domains
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Protein Transport
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Signal Transduction*
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Solubility
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Wnt Proteins / chemistry*
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Wnt Proteins / metabolism*
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Wnt1 Protein / chemistry
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Wnt1 Protein / metabolism
Substances
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Adaptor Proteins, Signal Transducing
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Cell Cycle Proteins
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Daxx protein, Drosophila
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Drosophila Proteins
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Fatty Acids, Monounsaturated
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Glypicans
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Lipids
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Nuclear Proteins
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TXNL4B protein, human
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Wnt Proteins
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Wnt1 Protein
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wg protein, Drosophila
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palmitoleic acid