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dc.contributor.authorCobbold, C
dc.contributor.authorCoventry, J
dc.contributor.authorPonnambalam, S
dc.contributor.authorMonaco, AP
dc.date.accessioned2017-05-03T15:03:56Z
dc.date.available2017-05-03T15:03:56Z
dc.date.issued2003
dc.date.modified2009-12-22T03:06:43Z
dc.identifier.issn0964-6906
dc.identifier.doi10.1093/hmg/ddg166
dc.identifier.urihttp://hdl.handle.net/10072/27902
dc.description.abstractThe Menkes disease gene encodes a P-type transmembrane ATPase (MNK) that translocates cytosolic copper ions across intracellular membranes of compartments along the secretory pathway. MNK moves from the trans-Golgi network (TGN) to the cell surface in response to exogenously added copper ions and recycles back to the TGN upon copper removal. The protein contains a C-terminal di-leucine motif necessary for internalization from the cell surface. In this study we show that MNK is internalized by a novel pathway that is independent of clathrin-mediated endocytosis. Expression of dominant-negative mutants of the dynamin-I and dynamin-II proteins that block clathrindependent endocytosis of the transferrin receptor, do not inhibit internalization of endogenous MNK, or a CD8-MCF1 reporter molecule. Similarly, inhibitors of caveolae-mediated uptake do not affect MNK internalization whilst preventing uptake of PODIPY-ganglioside GM1, a caveolae marker. In contrast, expression of a constitutively active mutant of the Rac1 GTPase inhibits plasma membrane internalization of both the MNK and transferrin receptor transmembrane proteins. Potential downstream effectors of Rac1-regulated MNK internalization are also analyzed. These findings define a novel route required for MNK internalization and delivery to endosomes.
dc.description.peerreviewedYes
dc.description.publicationstatusYes
dc.languageEnglish
dc.language.isoeng
dc.publisherOxford University Press
dc.publisher.placeOxford University
dc.publisher.urihttp://hmg.oxfordjournals.org/
dc.relation.ispartofpagefrom1523
dc.relation.ispartofpageto1533
dc.relation.ispartofissue13
dc.relation.ispartofjournalHuman Molecular Genetics
dc.relation.ispartofvolume12
dc.subject.fieldofresearchBiological sciences
dc.subject.fieldofresearchBiomedical and clinical sciences
dc.subject.fieldofresearchcode31
dc.subject.fieldofresearchcode32
dc.titleThe Menkes disease ATPase (ATP7A) is internalised via a Rac1-regulated, clathrin- and caveolae-independent pathway
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
gro.date.issued2003
gro.hasfulltextNo Full Text
gro.griffith.authorCobbold, Christian J.


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