dc.contributor.author | Cobbold, C | |
dc.contributor.author | Coventry, J | |
dc.contributor.author | Ponnambalam, S | |
dc.contributor.author | Monaco, AP | |
dc.date.accessioned | 2017-05-03T15:03:56Z | |
dc.date.available | 2017-05-03T15:03:56Z | |
dc.date.issued | 2003 | |
dc.date.modified | 2009-12-22T03:06:43Z | |
dc.identifier.issn | 0964-6906 | |
dc.identifier.doi | 10.1093/hmg/ddg166 | |
dc.identifier.uri | http://hdl.handle.net/10072/27902 | |
dc.description.abstract | The 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.peerreviewed | Yes | |
dc.description.publicationstatus | Yes | |
dc.language | English | |
dc.language.iso | eng | |
dc.publisher | Oxford University Press | |
dc.publisher.place | Oxford University | |
dc.publisher.uri | http://hmg.oxfordjournals.org/ | |
dc.relation.ispartofpagefrom | 1523 | |
dc.relation.ispartofpageto | 1533 | |
dc.relation.ispartofissue | 13 | |
dc.relation.ispartofjournal | Human Molecular Genetics | |
dc.relation.ispartofvolume | 12 | |
dc.subject.fieldofresearch | Biological sciences | |
dc.subject.fieldofresearch | Biomedical and clinical sciences | |
dc.subject.fieldofresearchcode | 31 | |
dc.subject.fieldofresearchcode | 32 | |
dc.title | The Menkes disease ATPase (ATP7A) is internalised via a Rac1-regulated, clathrin- and caveolae-independent pathway | |
dc.type | Journal article | |
dc.type.description | C1 - Articles | |
dc.type.code | C - Journal Articles | |
gro.date.issued | 2003 | |
gro.hasfulltext | No Full Text | |
gro.griffith.author | Cobbold, Christian J. | |