{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T09:32:48Z","timestamp":1777541568004,"version":"3.51.4"},"reference-count":42,"publisher":"American Society for Microbiology","issue":"1","license":[{"start":{"date-parts":[[2003,2,1]],"date-time":"2003-02-01T00:00:00Z","timestamp":1044057600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Eukaryot Cell"],"published-print":{"date-parts":[[2003,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            We have previously demonstrated that glycosylphosphatidylinositol (GPI) anchors strongly influence protein trafficking in the procyclic insect stage of\n            <jats:italic>Trypanosoma brucei<\/jats:italic>\n            (M. A. McDowell, D. A. Ransom, and J. D. Bangs, Biochem. J. 335:681-689, 1998), where GPI-minus variant surface glycoprotein (VSG) reporters have greatly reduced rates of endoplasmic reticulum (ER) exit but are ultimately secreted. We now demonstrate that GPI-dependent trafficking also occurs in pathogenic bloodstream trypanosomes. However, unlike in procyclic trypanosomes, truncated VSGs lacking C-terminal GPI-addition signals are not secreted but are mistargeted to the lysosome and degraded. Failure to export these reporters is not due to a deficiency in secretion of these cells since the N-terminal ATPase domain of the endogenous ER protein BiP is efficiently secreted from transgenic cell lines. Velocity sedimentation experiments indicate that GPI-minus VSG dimerizes similarly to wild-type VSG, suggesting that degradation is not due to ER quality control mechanisms. However, GPI-minus VSGs are fully protected from degradation by the cysteine protease inhibitor FMK024, a potent inhibitor of the major lysosomal protease trypanopain. Immunofluorescence of cells incubated with FMK024 demonstrates that GPI-minus VSG colocalizes with p67, a lysosomal marker. These data suggest that in the absence of a GPI anchor, VSG is mistargeted to the lysosome and subsequently degraded. Our findings indicate that GPI-dependent transport is a general feature of secretory trafficking in both stages of the life cycle. A working model is proposed in which GPI valence regulates progression in the secretory pathway of bloodstream stage trypanosomes.\n          <\/jats:p>","DOI":"10.1128\/ec.2.1.76-83.2003","type":"journal-article","created":{"date-parts":[[2003,2,11]],"date-time":"2003-02-11T23:36:19Z","timestamp":1045006579000},"page":"76-83","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":56,"title":["Glycosylphosphatidylinositol-Dependent Protein Trafficking in Bloodstream Stage\n            <i>Trypanosoma brucei<\/i>"],"prefix":"10.1128","volume":"2","author":[{"given":"Veronica P.","family":"Triggs","sequence":"first","affiliation":[{"name":"Department of Biomolecular Chemistry"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James D.","family":"Bangs","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Immunology, University of Wisconsin-Madison Medical School, Madison, Wisconsin 53706"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.115.16.3253"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.103.1.255"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.31.18387"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/16.14.4285"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/362603a0"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.115.4.805"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.cellbio.14.1.19"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(92)90189-J"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/0166-6851(89)90132-1"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.00-0415hyp"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-6851(01)00368-1"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/0166-6851(96)02706-5"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/mcb.8.2.674-678.1988"},{"key":"e_1_3_2_15_2","first-page":"344","volume":"34","year":"1987","unstructured":"Coppens, I., F. 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