| Summary: | Phosphoglucose isomerase (PGI) is a glycolytic enzyme that moonlights as a cellular
cytokine. The protein is also known as autocrine motility factor (AMF), neuroleukin and
maturation factor. PGI/AMF interaction with its receptor interaction is pH-dependent.
Indeed, at neutral pH, PGI/AMF binds its receptor AMFR at the cell surface and can be
endocytosed via two different pathways: caveolae/raft-dependent endocytosis to the
smooth ER or clathrin-dependent endocytosis to multivesicular bodies (MVBs).
Internalized PGI/AMF can recycle from MVBs to the plasma membrane where it can
undergo further rounds of endocytosis and recycling. Recycling receptor-ligand
complexes can also be sequestered via stable association with FN fibrils. Recent data
show that, at acid pH, endocytosis is inhibited and PGI/AMF binds directly to FN fibrils
or to HS. Heparan sulfate proteoglycans, when expressed on the surface of cells,
modulate the actions of a large number of extracellular ligands while fibronectin is
involved in many cellular processes such as tissue repair and cell migration/adhesion.
However, the mechanisms that regulate PGI/AMF binding to its receptors still remain
unclear.
PGI/AMF cytokine activity, associated with several diseases, has been reported in
rheumatoid synovial fluid and its deposition on synovial surfaces and ability to induce an
autoimmune response in rheumatoid arthritis (RA) identified it as a possible autoantigen
different from normal circulating PGI/AMF. However, more recent manuscripts have
questioned the prevalence of an autoimmune response to PGI in RA .
In this study, recombinant PGI constructs were used to characterize PGI interactions and
functions. We demonstrate that PGI behaves differently after N or C-terminal residue
additions. Our data also suggest that monomerization but not enzymatic activity is
necessary to induce cell motility at neutral pH. The putative function of PGI in RA was
assessed and using the recombinant PGI constructs and PGI autoantibodies was found to
be species and conformation-dependant. === Medicine, Faculty of === Graduate
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