AC. elegansZona Pellucida domain protein functions via its ZPc domain

Abstract

Zona Pellucida domain (ZP) proteins are critical components of the body’s 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.

C. elegans Apical Extracellular Matrices Shape Epithelia

“…Morphologically similar vesicles and spherically-expanding matrix packets have been seen by TEM within the vulF cells of the vulva [48]. The molecular nature of these vesicles is not known, but their cargo may include the ZP protein LET-653, which is capable of binding spherical aggregates in vitro [201].…”