title: Investigation of the adaptor protein PLIC-2 in multiple pathways.
abstract: PLIC, Protein Linking IAP (CD47) to Cytoskeleton, have long since been implicated in connecting the extracellular membrane to the intracellular cell cytoskeleton. This phenomenon is supposedly achieved by bridging a receptor protein CD47 to vimentin, an intermediate filament, which in turn regulates integrin dependent cell spreading. Since the discovery of these proteins, the molecular details of the above-mentioned interactions and the underlying complexes are yet to be characterized. Several independent studies have together emphasized PLIC/Ubiquilin's role in the proteasomal degradation pathway. This seems to be in contrast to the purported initial discovery of PLIC as a cytoskeletal adaptor protein. In an effort to reconcile the different roles associated with the ubiquitous PLIC proteins, we tested the involvement of PLIC-2 both in the proteasomal degradation pathway and as a protein linking the cell cytoskeleton to the cytoplasmic tail of CD47. This was achieved thorough an in vitro investigation of their binding interface using a combination of biophysical techniques. Our results show that the two terminal domains of PLIC-2 interact weakly with each other, while the C-terminal UBA domain interacts strongly with ubiquitin. Interestingly, no perceptible interaction was observed for PLIC-2 with the cytoplasmic tail of CD47 questioning its role as a "PLIC" protein linking the cell membrane to the cytoskeleton.
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, University of Connecticut at Storrs, Storrs, CT 06269.
authors.forename: Khiem
authors.initials: K
authors.lastname: Nguyen
authors.affiliation: Department of Molecular and Cell Biology, CLAS, University of Connecticut at Storrs, Storrs, CT 06269.
authors.forename: Robbins
authors.initials: R
authors.lastname: Puthenveetil
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, University of Connecticut at Storrs, Storrs, CT 06269.
authors.forename: Olga
authors.initials: O
authors.lastname: Vinogradova
keywords: CD47; ITC; NMR; PLIC; UBA; UBL; Ubiquilin; Vimentin; cytoplasmic tail; membrane proteins; nanodisc; proteasomal degradation; transmembrane