Biology subjects

Sundaram, M. V.

Publications and source records attributed to Sundaram, M. V..

3 recordsLinked to original sources

bioRxiv2021

The C. elegans PTCHD homolog PTR-4 is required for proper organization of the pre-cuticular apical extracellular matrix

The Patched-related (PTR) superfamily of transmembrane proteins can transport lipids or other hydrophobic molecules across cell membranes. While the hedgehog receptor Patched has been intensively studied, much less is known about the biological roles of other PTR or Patched domain (PTCHD) family members. C. elegans has a large number of PTR/PTCHD proteins, despite lacking a canonical hedgehog pathway. Here, we show that PTR-4 promotes the assembly of the pre-cuticle apical extracellular matrix (aECM), a transient and molecularly distinct aECM that precedes and patterns the later collagenous cuticle or exoskeleton. ptr-4 mutants share many phenotypes with pre-cuticle mutants, including defects in eggshell dissolution, tube shaping, alae (cuticle ridge) structure, and cuticle barrier function. PTR-4 localizes to the apical side of a subset of outward-facing epithelia, in a cyclical manner that peaks when pre-cuticle matrix is present. Finally, PTR-4 acts in a cell non-autonomous manner to properly localize the secreted ZP domain protein LET-653 to the pre-cuticle aECM. We propose that PTR-4 exports lipids or other hydrophobic components of the pre-cuticle aECM.

cell biology↗

bioRxiv2020

A C. elegans Zona Pellucida domain protein functions via its ZPc domain

Zona Pellucida domain (ZP) proteins are critical components of the bodys external-most protective layers, apical extracellular matrices (aECMs). Although their loss or dysfunction is associated with many diseases, it remains unclear how ZP proteins assemble in aECMs. Current models suggest that ZP proteins polymerize via their ZPn subdomains, while ZPc subdomains modulate ZPn behavior. Using the model organism C. elegans, we investigated the aECM assembly of one ZP protein, LET-653, which shapes several tubes. Contrary to prevailing models, we find that LET-653 localizes and functions via its ZPc domain. Furthermore, the ZPc domain is inhibited by the ZPn domain and cleavage of the LET-653 C-terminus relieves this inhibition. In vitro, the ZPc, but not ZPn, domain formed crystalline aggregates. These data offer a new model for ZP function whereby the ZPc domain is primarily responsible for matrix incorporation and tissue shaping.

genetics↗

bioRxiv2020

A multi-layered and dynamic apical extracellular matrix shapes the vulva lumen in Caenorhabditis elegans

Biological tubes must develop and maintain their proper diameter in order to transport materials efficiently. These tubes are molded and protected in part by apical extracellular matrices (aECMs) that line their lumens. Despite their importance, aECMs are difficult to image in vivo and therefore poorly understood. The C. elegans vulva has been a paradigm for understanding many aspects of organogenesis. Here we describe the vulva luminal matrix, which contains chondroitin proteoglycans, Zona Pellucida (ZP) domain proteins, and other glycoproteins and lipid transporters related to those in mammals. Confocal and transmission electron microscopy revealed, with unprecedented detail, a complex and dynamic aECM. Different matrix factors assemble on the apical surfaces of each vulva cell type, with clear distinctions seen between Ras-dependent (1{degrees}) and Notch-dependent (2{degrees}) cell types. Genetic perturbations suggest that chondroitin and other aECM factors together generate a structured scaffold that both expands and constricts lumen shape.

developmental biology↗