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dc.contributor.authorMullin, KA
dc.contributor.authorFoth, BJ
dc.contributor.authorIlgoutz, SC
dc.contributor.authorCallaghan, JM
dc.contributor.authorZawadzki, JL
dc.contributor.authorMcFadden, GI
dc.contributor.authorMcConville, MJ
dc.date.available2014-05-21T19:36:52Z
dc.date.issued2001-08-01
dc.identifierhttp://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000170715900010&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=d4d813f4571fa7d6246bdc0dfeca3a1c
dc.identifier.citationMullin, K. A., Foth, B. J., Ilgoutz, S. C., Callaghan, J. M., Zawadzki, J. L., McFadden, G. I. & McConville, M. J. (2001). Regulated degradation of an endoplasmic reticulum membrane protein in a tubular lysosome in Leishmania mexicana. MOLECULAR BIOLOGY OF THE CELL, 12 (8), pp.2364-2377. https://doi.org/10.1091/mbc.12.8.2364.
dc.identifier.issn1059-1524
dc.identifier.urihttp://hdl.handle.net/11343/26535
dc.descriptionC1 - Journal Articles Refereed
dc.description.abstractThe cell surface of the human parasite Leishmania mexicana is coated with glycosylphosphatidylinositol (GPI)-anchored macromolecules and free GPI glycolipids. We have investigated the intracellular trafficking of green fluorescent protein- and hemagglutinin-tagged forms of dolichol-phosphate-mannose synthase (DPMS), a key enzyme in GPI biosynthesis in L. mexicana promastigotes. These functionally active chimeras are found in the same subcompartment of the endoplasmic reticulum (ER) as endogenous DPMS but are degraded as logarithmically growing promastigotes reach stationary phase, coincident with the down-regulation of endogenous DPMS activity and GPI biosynthesis in these cells. We provide evidence that these chimeras are constitutively transported to and degraded in a novel multivesicular tubule (MVT) lysosome. This organelle is a terminal lysosome, which is labeled with the endocytic marker FM 4-64, contains lysosomal cysteine and serine proteases and is disrupted by lysomorphotropic agents. Electron microscopy and subcellular fractionation studies suggest that the DPMS chimeras are transported from the ER to the lumen of the MVT via the Golgi apparatus and a population of 200-nm multivesicular bodies. In contrast, soluble ER proteins are not detectably transported to the MVT lysosome in either log or stationary phase promastigotes. Finally, the increased degradation of the DPMS chimeras in stationary phase promastigotes coincides with an increase in the lytic capacity of the MVT lysosome and changes in the morphology of this organelle. We conclude that lysosomal degradation of DPMS may be important in regulating the cellular levels of this enzyme and the stage-dependent biosynthesis of the major surface glycolipids of these parasites.
dc.formatapplication/pdf
dc.languageEnglish
dc.publisherAMER SOC CELL BIOLOGY
dc.subjectProtein Targeting and Signal Transduction; Infectious Agents; Infectious Diseases
dc.titleRegulated degradation of an endoplasmic reticulum membrane protein in a tubular lysosome in Leishmania mexicana
dc.typeJournal Article
dc.identifier.doi10.1091/mbc.12.8.2364
melbourne.peerreviewPeer Reviewed
melbourne.affiliationThe University of Melbourne
melbourne.affiliation.departmentBiochemistry And Molecular Biology
melbourne.source.titleMolecular Biology of the Cell
melbourne.source.volume12
melbourne.source.issue8
melbourne.source.pages2364-2377
melbourne.publicationid1105
melbourne.elementsid247228
melbourne.openaccess.pmchttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC58600
melbourne.contributor.authorMcFadden, Geoffrey
melbourne.contributor.authorMcConville, Malcolm
melbourne.contributor.authorMULLIN, KYLIE
melbourne.contributor.authorCALLAGHAN, JUDITH
melbourne.contributor.authorFOTH, BERNARDO JAVIER
melbourne.contributor.authorIlgoutz, Steven
melbourne.contributor.authorZAWADZKI, JODY LOUISE
dc.identifier.eissn1939-4586
melbourne.accessrightsAccess this item via the Open Access location


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