Rotavirus (RV) is an etiologic agent of viral gastroenteritis in children and infants
worldwide, accounting for an estimated 500,000 deaths annually. NSP4, the first
described viral enterotoxin, contributes to RV pathogenesis by mobilizing intracellular
calcium through multiple mechanisms that promote abnormal ion transport and
subsequent secretory diarrhea. NSP4 and the enterotoxic peptide 114-135 preferentially
interact with model membranes mimicking caveolae in lipid composition and radius of
curvature. Our laboratory has recently reported the colocalization and
coimmunoprecipitation of NSP4 with caveolin-1, the structural protein of caveolae.
Moreover, the caveolin-1 binding domain of NSP4 has been localized to the enterotoxic
peptide. We now report that caveolin-1 binds NSP4 via the N- and C-termini and one
terminus is sufficient for binding. A panel of caveolin-1 deletion mutants was expressed
in a yeast two-hybrid assay against an NSP4 bait. Caveolin-1 mutants retaining at least
one terminus were capable of binding the NSP4 bait. An in vitro binding assay
confirmed the two-hybrid results and localized the NSP4 binding domains to caveolin-1
residues 2-22 and 161-178. These data support the hypothesis that caveolin-1 mediates
NSP4 signaling and/or intracellular trafficking.
| Identifer | oai:union.ndltd.org:tamu.edu/oai:repository.tamu.edu:1969.1/3976 |
| Date | 16 August 2006 |
| Creators | Mir, Kiran D |
| Contributors | Ball, Judith M. |
| Publisher | Texas A&M University |
| Source Sets | Texas A and M University |
| Language | en_US |
| Detected Language | English |
| Type | Book, Thesis, Electronic Thesis, text |
| Format | 819617 bytes, electronic, application/pdf, born digital |
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