A Lipocalin and a Hedgehog-related protein are partners in the C. elegans pre-cuticle apical extracellular matrix

Apical extracellular matrices (aECMs) line exposed body surfaces to shape tissues and protect them from the environment. These aECMs often organize into complex patterns and structures, but how such matrices assemble remains poorly understood. Caenorhabditis elegans cuticle patterns initiate within the transient pre-cuticle, which then helps direct the placement of cuticle collagens. Pre-cuticle patterns arise through post-secretory sorting, which must involve specific molecular interactions among them. Consistent with such a model, Alphafold3 predicts a high confidence physical interaction between two pre-cuticle proteins, the lipocalin LPR-3 and the Hedgehog-related protein WRT-10, with a conserved N-terminal region of LPR-3 forming a {beta}-strand that incorporates into the {beta}-barrel-like structure of the WRT-10 WRT domain. Genetic studies showed that WRT-10 requires this LPR-3 region in order to become properly patterned in the pre-cuticle matrix. Furthermore, WRT-10 and the LPR-3 {beta}-strand region are required to pattern a specific cuticle substructure, the lateral alae ridges, but not for other LPR-3-dependent matrix roles. These data indicate that LPR-3 and WRT-10 are functional partners and support a "landing pad" model whereby physical interactions between them allow LPR-3 to recruit WRT-10 to specific aECM regions. Similar mechanisms may explain how other members of the C. elegans Hh-r family associate with the aECM. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=100 SRC="FIGDIR/small/739337v1_ufig1.gif" ALT="Figure 1"> View larger version (22K): org.highwire.dtl.DTLVardef@18c3601org.highwire.dtl.DTLVardef@2da36dorg.highwire.dtl.DTLVardef@4461d1org.highwire.dtl.DTLVardef@171e287_HPS_FORMAT_FIGEXP M_FIG C_FIG Article SummaryAll animal skin is covered by a set of proteins, sugars and lipids that comprise the apical extracellular matrix (aECM). These matrix components can be organized into patterned ridges and other distinctive structures. This study addresses how such patterns form in the developing cuticle of the nematode C. elegans. The study provides evidence for a regulatory mechanism that enables one matrix protein to establish a pattern and then recruit a second protein into the same pattern.