The rotavirus surface protein VP8 modulates the gate and fence function of tight junctions in epithelial cells


Por: Nava P., López S., Arias C.F., Islas S., González-Mariscal L.

Publicada: 1 ene 2004
Resumen:
Rotaviruses constitute a major cause of diarrhea in young mammals. Rotaviruses utilize different integrins as cell receptors, therefore upon their arrival to the intestinal lumen their integrin receptors will be hidden below the tight junction (TJ), on the basolateral membrane. Here we have studied whether the rotavirus outer capsid proteins are capable of opening the paracellular space sealed by the TJ. From the outermost layer of proteins of the rotavirus, 60 spikes formed of protein VP4 are projected. VP4 is essential for virus-cell interactions and is cleaved by trypsin into peptides VP5 and VP8. Here we found that when these peptides are added to confluent epithelial monolayers (Madin-Darby canine kidney cells), VP8 is capable of diminishing in a dose dependent and reversible manner the transepithelial electrical resistance. VP5 exerted no effect. VP8 can also inhibit the development of newly formed TJs in a Ca-switch assay. Treatment with VP8 augments the paracellular passage of non-ionic tracers, allows the diffusion of a fluorescent lipid probe and the apical surface protein GP135, from the luminal to the lateral membrane, and triggers the movement of the basolateral proteins Na+-K+-ATPase, ?v?3 integrin and ?1 integrin subunit, to the apical surface. VP8 generates a freeze-fracture pattern of TJs characterized by the appearance of loose end filaments, that correlates with an altered distribution of several TJ proteins. VP8 given orally to diabetic rats allows the enteral administration of insulin, thus indicating that it can be employed to modulate epithelial permeability.

Filiaciones:
Nava P.:
 Dept. of Physiol. Biophys./Neurosci., Ctr. for Research/Advanced Studies, CINVESTAV, Mexico D.F. 07000, Mexico

López S.:
 Dept. Devmtl. Genet./Molec. Physiol., Institute of Biotechnology, National University of Mexico, Cuernavaca, Morelos 62250, Mexico

Arias C.F.:
 Dept. Devmtl. Genet./Molec. Physiol., Institute of Biotechnology, National University of Mexico, Cuernavaca, Morelos 62250, Mexico

Islas S.:
 Dept. of Physiol. Biophys./Neurosci., Ctr. for Research/Advanced Studies, CINVESTAV, Mexico D.F. 07000, Mexico

González-Mariscal L.:
 Dept. of Physiol. Biophys./Neurosci., Ctr. for Research/Advanced Studies, CINVESTAV, Mexico D.F. 07000, Mexico
ISSN: 00219533
Editorial
COMPANY OF BIOLOGISTS LTD, BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND, Reino Unido
Tipo de documento: Article
Volumen: 117 Número: 23
Páginas: 5509-5519
WOS Id: 000225672900007
ID de PubMed: 15494377
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