Study of vaults in skin biology and host defence - from in vitro to in vivo

• Main Author: Lian, Yilong
• Other Authors: Sara Sandin
• Format: Theses and Dissertations
• Language: English
• Published: 2019
• Subjects: DRNTU::Science::Biological sciences::Molecular biology
• Online Access: https://hdl.handle.net/10356/95071; http://hdl.handle.net/10220/48569
• Institution: Nanyang Technological University

Vault, an approximately 13 MDa ribonucleoprotein first isolated from rat liver, consists of 3 proteins, TEP1, vPARP and MVP, and a group of non-coding RNAs known as vtRNAs. Vault particles have a capsular barrel-like structure which can be formed by MVP alone. MVP, the structural protein of vaults, is its most well-studied component. MVP is highly conserved amongst eukaryotes. Yet, according to genomic sequence analysis, MVP is missing in some lineages including model organisms such as C. elegans, D. melanogaster and S. cerevisiae. Despite the involvement of MVP in a wide variety of cellular functions such as signalling stress responses and immune responses, its biological function remains unknown. Using a combination of zebrafish and cell lines, the expression and localisation of MVP under basal and stimulated conditions were characterised in an attempt to elucidate the function(s) of vaults. MVP expression was enriched in the epithelial tissues of zebrafish larvae. Upregulation of krt8, krt18 and eppk1, which are involved in stress responses, was observed in developing mvp-/- larvae. In studies using cell lines, cytoplasmic staining pattern of MVP in cells was observed. When mammalian cells were treated with bacteria, a novel extracellular interaction of MVP with these bacteria was observed. This interaction was also observed between a truncated MVP fragment in plasma, and bacteria. These interactions were found in various bacteria. In particular, Psl of P. aeruginosa was shown to be responsible for the binding to MVP. Binding of MVP to P. aeruginosa did not affect the survival of bacteria but seemed to affect the aggregation of P. aeruginosa. These results suggest that MVP is upregulated by the presence of bacteria and acts as a sentinel of the innate immune response, modulating host-pathogen responses.