Investigation of Glycosylphosphatidylinositol (GPI) Anchorage and GPI-Anchored Proteins

University Of Florida, Gainesville FL

Investigators

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Abstract

Program Director/Principal Investigator (Last, First, Middle): GUO, Zhongwu Investigation of Glycosylphosphatidylinositol (GPI) Anchorage and GPI-Anchored Proteins Glycosylphosphatidylinositol (GPI) linkage to the protein C-terminus is one of the most common and important post-translational modifications. GPI-linked proteins are anchored onto the outer leaflet of the cell membrane to play a critical role in various physiological and pathological processes, such as cellular recognition, adhesion and signaling. However, in-depth investigations of GPI anchors and GPI-anchored proteins (GPI-APs) are challenging, largely because of their complex and diverse structures and amphipathic property as well as the lack of appropriate research tools and methods to study GPIs and GPI-APs. The goal of this project is to overcome the challenges by developing new probes, including efficient methods for the synthesis of these probes, and research methods to facilitate GPI/GPI-AP investigation and fill out an important scientific gap. Specifically, the future research directions of this project will include: 1) developing new molecular tools, including both DNA/RNA aptamers and fluorescent DNA probes, and methods for sensitive GPI detection to facilitate studies of GPI-APs on live cells; 2) developing new probes and methods for GPI-AP labeling and isolation to enable their characterization and high throughput analysis, and examining GPI-anchored proteomics expressed by different cells to discover new molecular markers; 3) developing new probes and methods to enable the study of the membrane organization and other biophysical properties of GPIs/GPI-APs, and exploring the mechanisms by which GPI-APs act as mechanotransducers in various binding and signaling events; 4) developing new probes and research methods to enable studies of GPI-cell membrane interaction, and identifying GPI-binding proteins in the cell membrane involved in GPI-mediated signaling and other processes like GPI-AP trafficking. This project is innovative and will have a big and broad impact, since it addresses several important, unresolved challenges associated with GPI-AP research and helps comprehend the biological significances of GPI anchorage at large. Particularly, through systematic and in-depth investigations, it will allow access to a diversity of probes and research methods for biological studies of GPIs/GPI-APs and provide useful information about the organization of GPIs/GPI-APs on the cell surface, GPI binding with other biomolecules in the cell membrane, and GPI-anchored proteomics. The results will not only help better understand the functional roles and mechanisms of GPIs and GPI- APs in various biological processes but also help uncover novel GPI-APs and GPI-interacting proteins related to cellular recognition and signal transduction and novel biomarkers useful for development of innovative diagnostic and therapeutic strategies for human diseases. OMB No. 0925-0001/0002 (Rev. 10/2021 Approved Through 01/31/2026) Page Continuation Format Page