N4WBP5A (Ndfip2), a Nedd4-interacting protein, localizes to multivesicular bodies and the Golgi, and has a potential role in protein trafficking

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dc.contributor.authorShearwin-Whyatt, L.
dc.contributor.authorBrown, D.
dc.contributor.authorWylie, F.
dc.contributor.authorStow, J.
dc.contributor.authorKumar, S.
dc.date.issued2004
dc.description.abstractN4WBP5A (Ndfip2) belongs to an evolutionarily conserved group of Nedd4-interacting proteins with two homologues in mammalian species. We have previously shown that N4WBP5A expression in Xenopus oocytes results in increased cell-surface expression of the epithelial sodium channel. N4WBPs are characterized by one or two amino terminal PPxY motifs and three transmembrane domains. Here we show that both PPxY motifs of N4WBP5A mediate interaction with WW domains of Nedd4 and that N4WBP5A can physically interact with the WW domains of several Nedd4-family proteins. N4WBP5A is ubiquitinated and ubiquitination does not significantly affect the turnover of N4WBP5A protein. Ubiquitination of N4WBP5A is enhanced by Nedd4 and Nedd4-2 expression. N4WBP5A localizes to the Golgi, vesicles associated with the Golgi complex and to multivesicular bodies. We show that the ectopic expression of N4WBP5A inhibits receptor-mediated endocytosis of labelled epidermal growth factor. N4WBP5A overexpression inhibits accumulation of EGF in large endocytic/lysosomal vesicles suggestive of a role for N4WBP5A in protein trafficking. We propose that N4WBP5A acts as an adaptor to recruit Nedd4 family ubiquitin-protein ligases to the protein trafficking machinery.
dc.description.statementofresponsibilityLinda M. Shearwin-Whyatt, Darren L. Brown, Fiona G. Wylie, Jennifer L. Stow and Sharad Kumar
dc.identifier.citationJournal of Cell Science, 2004; 117(16):3679-3689
dc.identifier.doi10.1242/jcs.01212
dc.identifier.issn0021-9533
dc.identifier.issn1477-9137
dc.identifier.orcidShearwin-Whyatt, L. [0000-0002-4504-6534]
dc.identifier.orcidKumar, S. [0000-0001-7126-9814]
dc.identifier.urihttp://hdl.handle.net/2440/9578
dc.language.isoen
dc.publisherCompany of Biologists Ltd
dc.rights© The Company of Biologists Limited 2004
dc.source.urihttp://jcs.biologists.org/cgi/content/abstract/117/16/3679
dc.subjectNedd4
dc.subjectUbiquitination
dc.subjectWW domains
dc.subjectMultivesicular bodies
dc.titleN4WBP5A (Ndfip2), a Nedd4-interacting protein, localizes to multivesicular bodies and the Golgi, and has a potential role in protein trafficking
dc.typeJournal article
pubs.publication-statusPublished

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