Biology subjects

Birnbaum, S. K.

Publications and source records attributed to Birnbaum, S. K..

3 recordsLinked to original sources

bioRxiv2026

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@1fdaf57org.highwire.dtl.DTLVardef@2b752org.highwire.dtl.DTLVardef@51a91forg.highwire.dtl.DTLVardef@13665ad_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.

developmental biology↗

bioRxiv2026

Pre-cuticle DPY 6 acts as a blueprint for aECM periodic organization in C. elegans

Apical extracellular matrices (aECMs) are essential for tissue integrity and function in multicellular organisms, but there is limited understanding of how such matrices are assembled and organized in the extracellular environment. The Caenorhabditis elegans cuticle, a model aECM that undergoes morphogenesis during each of the worms four larval molts, requires periodic circumferential furrows for structural integrity and immune regulation. Here, we show that furrow collagens must be cleaved from their N-terminal transmembrane domain for secretion and depend on the mucin-like pre-cuticle protein DPY-6 for their periodic assembly. While DPY-6 is dispensable for initial embryonic furrow formation, it acts as a mold during subsequent molts, ensuring pattern replication via its C-terminal cysteine cradle domain. These results reveal a central role for a transient matrix factor in organizing a complex periodically structured aECM. Author SummaryIn multicellular organisms, the extracellular matrix (ECM) provides structural support and regulates tissue function. Using the free-living worm Caenorhabditis elegans, we investigated how its apical ECM, the cuticle, forms a precise, repeating pattern of ridges called furrows. The cuticle is rebuilt at each of the worms four larval stages, providing a unique opportunity to study matrix morphogenesis in real time. We discovered that a transient protein, DPY-6, acts as a molecular mold to guide the self-organization of the matrix outside the epidermal cells. DPY-6 ensures that newly secreted proteins assemble into the correct periodic pattern during each rebuilding phase. Without DPY-6, the furrows lose their organization, leading to structural defects and immune system activation. Our findings reveal how a temporary scaffold can template the assembly of a complex, self-organizing structure. This work provides new insights into how biological matrices are built and maintained, with broader implications for understanding ECM assembly in health and disease.

developmental biology↗

bioRxiv2023

The proprotein convertase BLI-4 promotes collagen secretion during assembly of the Caenorhabditis elegans cuticle

Some types of collagens, including transmembrane MACIT collagens and C. elegans cuticle collagens, are N-terminally cleaved at a dibasic site that resembles the consensus for furin or other proprotein convertases of the subtilisin/kexin (PCSK) family. Such cleavage may release transmembrane collagens from the plasma membrane and affect extracellular matrix assembly or structure. However, the functional consequences of such cleavage are unclear and evidence for the role of specific PCSKs is lacking. Here, we used endogenous collagen fusions to fluorescent proteins to visualize the secretion and assembly of the first collagen-based cuticle in C. elegans and then tested the role of the PCSK BLI-4 in these processes. Unexpectedly, we found that cuticle collagens SQT-3 and DPY-17 are secreted into the extraembryonic space several hours before cuticle matrix assembly. Furthermore, this early secretion depends on BLI-4/PCSK; in bli-4 and cleavage-site mutants, SQT-3 and DPY-17 are not efficiently secreted and instead form large intracellular aggregates. Their later assembly into cuticle matrix is reduced but not entirely blocked. These data reveal a role for collagen N-terminal processing in intracellular trafficking and in the spatial and temporal restriction of matrix assembly in vivo. Our observations also prompt a revision of the classic model for C. elegans cuticle matrix assembly and the pre-cuticle-to-cuticle transition, suggesting that cuticle layer assembly proceeds via a series of regulated steps and not simply by sequential secretion and deposition.

cell biology↗