TheC. elegansPTCHD homolog PTR-4 is required for proper organization of the pre-cuticular apical extracellular matrix

Abstract

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.

Homeostatic control of stearoyl desaturase expression via patched-like receptor PTR-23 ensures the survival of C. elegans during heat stress

“…Catillo et al reported that PTC-3, a C. elegans patched homolog, regulates lipid homeostasis and controls cellular cholesterol levels by acting as a cholesterol transporter [41]. Patched receptors share homology with bacterial RND transporters, and PTR-4, in particular, may act as a transporter of hydrophobic molecules, suggesting that patched/PTR proteins are transmembrane pumps for hydrophobic cargos [55]. PTR-23 might also be a lipid transporter.…”