Year: 2020
Type: article
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, we show that ZPc domain function requires cleavage at the LET-653 C-terminus, likely in part to relieve inhibition of the ZPc by the ZPn domain, but also to promote some other aspect of ZPc domain function. In vitro, the ZPc, but not ZPn, domain bound crystalline aggregates. These data offer a new model for ZP function whereby the ZPc domain is primarily responsible for matrix incorporation and tissue shaping.
Source: PLoS Genetics
Institution: University of Pennsylvania
Language: English
Subfield: Cell Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,500
Funders: National Science Foundation, University of Pennsylvania, National Institutes of Health, National Science Foundation of Sri Lanka, National Institute of General Medical Sciences, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institute of Biomedical Imaging and Bioengineering
Awards: G1461678227, Materials Research Science and Engineering Center, Regulation of the Timing and Spatial Patterning of Zygotic Genome Activation During Embryogenesis, G2111793168, Lipocalin-dependent glycocalyx organization and tube protection, G3317661987, Predoctoral Training Program in Genetics, Programmable Synthetic Organelles Built from Disordered Proteins for Cellular Engineering, Ras Signaling and Tubulogenesis in the C. elegans Excretory (renal) System, G6541575914, G9000028377, G9000300987, Caenorhabditis Genetics Center, Building and shaping the apical extracellular matrix, Penn Dermatology Research Training Program
OpenAlex ID: W3094824097