A lipocalin and a Hedgehog-related protein are partners in the Caenorhabditis elegans precuticle apical extracellular matrix
Abstract
Apical extracellular matrices line exposed body surfaces to shape tissues and protect them from the environment. These apical extracellular matrices often organize into complex patterns and structures, but how such matrices assemble remains poorly understood. Caenorhabditis elegans cuticle patterns initiate within the transient precuticle, which then helps direct the placement of cuticle collagens. Precuticle patterns arise through postsecretory sorting, which must involve specific molecular interactions among them. Consistent with such a model, Alphafold3 predicts a high confidence physical interaction between 2 precuticle proteins, the lipocalin LPR-3 and the Hedgehog-related protein WRT-10, with a conserved N-terminal region of LPR-3 forming a β-strand that incorporates into the β-sandwich structure of the WRT-10 WRT domain. Genetic studies showed that WRT-10 requires this LPR-3 region to become properly patterned in the precuticle matrix. Furthermore, WRT-10 and the LPR-3 β-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 in which physical interactions between them allow LPR-3 to recruit WRT-10 to specific apical extracellular matrix regions. Similar mechanisms may explain how other members of the C. elegans Hedgehog-related family associate with apical extracellular matrices.
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BibTeX
@article{serra2026lipocalin,
title = {{A lipocalin and a Hedgehog-related protein are partners in the Caenorhabditis elegans precuticle apical extracellular matrix}},
author = {Nicholas D Serra and Jason Chen and Susanna K Birnbaum and Sage G Aviles and Meera V Sundaram},
journal = {Genetics},
year = {2026},
month = aug,
doi = {10.1093/genetics/iyag218},
url = {https://doi.org/10.1093/genetics/iyag218},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - A lipocalin and a Hedgehog-related protein are partners in the Caenorhabditis elegans precuticle apical extracellular matrix
AU - Nicholas D Serra
AU - Jason Chen
AU - Susanna K Birnbaum
AU - Sage G Aviles
AU - Meera V Sundaram
PY - 2026
DA - 2026/08/19
JO - Genetics
DO - 10.1093/genetics/iyag218
UR - https://doi.org/10.1093/genetics/iyag218
AB - Apical extracellular matrices line exposed body surfaces to shape tissues and protect them from the environment. These apical extracellular matrices often organize into complex patterns and structures, but how such matrices assemble remains poorly understood. Caenorhabditis elegans cuticle patterns initiate within the transient precuticle, which then helps direct the placement of cuticle collagens. Precuticle patterns arise through postsecretory sorting, which must involve specific molecular interactions among them. Consistent with such a model, Alphafold3 predicts a high confidence physical interaction between 2 precuticle proteins, the lipocalin LPR-3 and the Hedgehog-related protein WRT-10, with a conserved N-terminal region of LPR-3 forming a β-strand that incorporates into the β-sandwich structure of the WRT-10 WRT domain. Genetic studies showed that WRT-10 requires this LPR-3 region to become properly patterned in the precuticle matrix. Furthermore, WRT-10 and the LPR-3 β-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 in which physical interactions between them allow LPR-3 to recruit WRT-10 to specific apical extracellular matrix regions. Similar mechanisms may explain how other members of the C. elegans Hedgehog-related family associate with apical extracellular matrices.
SN - 0016-6731
SN - 1943-2631
ER -