{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T22:15:33Z","timestamp":1791238533787,"version":"4.1.0"},"reference-count":43,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Traffic"],"published-print":{"date-parts":[[2015,10]]},"abstract":"The lysosomal integral membrane protein type 2 (LIMP<\/jats:styled-content>\u20102\/SCARB2<\/jats:styled-content>) has been described as a mannose 6\u2010phosphate (M6P<\/jats:styled-content>)\u2010independent trafficking receptor for \u03b2\u2010glucocerebrosidase (GC<\/jats:styled-content>). Recently, a putative M6P<\/jats:styled-content> residue in a crystal structure of a recombinantly expressed LIMP<\/jats:styled-content>\u20102 ectodomain has been reported. Based on surface plasmon resonance and fluorescence lifetime imaging analyses, it was suggested that the interaction of soluble LIMP<\/jats:styled-content>\u20102 with the cation\u2010independent M6P<\/jats:styled-content> receptor (MPR<\/jats:styled-content>) results in M6P<\/jats:styled-content>\u2010dependent targeting of LIMP<\/jats:styled-content>\u20102 to lysosomes. As the physiological relevance of this observation was not addressed, we investigated M6P<\/jats:styled-content>\u2010dependent delivery of LIMP<\/jats:styled-content>\u20102 to lysosomes in murine liver and mouse embryonic fibroblasts. We demonstrate that LIMP<\/jats:styled-content>\u20102 and GC<\/jats:styled-content> reach lysosomes independent of the M6P<\/jats:styled-content> pathway. In fibroblasts lacking either MPRs<\/jats:styled-content> or the M6P<\/jats:styled-content>\u2010forming N\u2010acetylglucosamine (GlcNAc<\/jats:styled-content>)\u20101\u2010phosphotransferase, LIMP<\/jats:styled-content>\u20102 still localizes to lysosomes. Immunoblot analyses also revealed comparable LIMP<\/jats:styled-content>\u20102 levels within lysosomes purified from liver of wild\u2010type (wt) and GlcNAc<\/jats:styled-content>\u20101\u2010phosphotransferase\u2010defective mice. Heterologous expression of the luminal domain of LIMP<\/jats:styled-content>\u20102 in wild\u2010type, LIMP<\/jats:styled-content>\u20102\u2010deficient and GlcNAc<\/jats:styled-content>\u20101\u2010phosphotransferase\u2010defective cells further established that the M6P<\/jats:styled-content> modification is dispensable for lysosomal sorting of LIMP<\/jats:styled-content>\u20102. Finally, cathepsin Z, a known GlcNAc<\/jats:styled-content>\u20101\u2010phosphotransferase substrate, but not LIMP<\/jats:styled-content>\u20102, could be precipitated with M6P<\/jats:styled-content>\u2010specific antibodies. These data prove M6P<\/jats:styled-content>\u2010independent lysosomal sorting of LIMP<\/jats:styled-content>\u20102 and subsequently GC in vivo.<\/jats:italic><\/jats:p><\/jats:p>","DOI":"10.1111\/tra.12313","type":"journal-article","created":{"date-parts":[[2015,7,29]],"date-time":"2015-07-29T10:27:34Z","timestamp":1438165654000},"page":"1127-1136","source":"Crossref","is-referenced-by-count":39,"title":["Mannose 6\u2010phosphate\u2010independent Lysosomal Sorting of LIMP<\/scp>\u20102"],"prefix":"10.1111","volume":"16","author":[{"given":"Judith","family":"Blanz","sequence":"first","affiliation":[{"name":"Biochemisches Institut der Christian Albrechts Universit\u00e4t zu Kiel Otto\u2010Hahn\u2010Platz 9 24118 Kiel Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Friederike","family":"Zunke","sequence":"additional","affiliation":[{"name":"Biochemisches Institut der Christian Albrechts Universit\u00e4t zu Kiel Otto\u2010Hahn\u2010Platz 9 24118 Kiel Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Markmann","sequence":"additional","affiliation":[{"name":"Arbeitsbereich Molekularbiologie, Klinik und Poliklinik f\u00fcr Kinder\u2010 und Jugendmedizin Universit\u00e4tsklinikum Hamburg\u2010Eppendorf Hamburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Damme","sequence":"additional","affiliation":[{"name":"Biochemisches Institut der Christian Albrechts Universit\u00e4t zu Kiel Otto\u2010Hahn\u2010Platz 9 24118 Kiel Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Braulke","sequence":"additional","affiliation":[{"name":"Arbeitsbereich Molekularbiologie, Klinik und Poliklinik f\u00fcr Kinder\u2010 und Jugendmedizin Universit\u00e4tsklinikum Hamburg\u2010Eppendorf Hamburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Saftig","sequence":"additional","affiliation":[{"name":"Biochemisches Institut der Christian Albrechts Universit\u00e4t zu Kiel Otto\u2010Hahn\u2010Platz 9 24118 Kiel Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Schwake","sequence":"additional","affiliation":[{"name":"Biochemie III\/ Fakult\u00e4t f\u00fcr Chemie Universit\u00e4t Bielefeld Universit\u00e4tsstr. 25 33615 Bielefeld Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,9]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2008.10.016"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.157.3790.804"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-4827(88)90472-7"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-291X(82)91042-7"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.10.018"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddp523"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature12684"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0854.2012.01372.x"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2007.12.019"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.21765"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2012.00032"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.1992"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms5321"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/aws209"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/cyto.a.20896"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.117.2.311"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.102.5.1593"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2006.04271.x"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.37.2.482"},{"key":"e_1_2_6_21_1","first-page":"140","article-title":"Effect of the injection of Triton WR 1339 on the hepatic lysosomes of the rat","volume":"71","author":"Wattiaux R","year":"1963","journal-title":"Arch Int Physiol Biochim"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2006.09.029"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M114.584144"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.290.5500.2298"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M500131-JLR200"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/17.5.1304"},{"key":"e_1_2_6_27_1","doi-asserted-by":"crossref","first-page":"16269","DOI":"10.1016\/S0021-9258(18)55288-1","article-title":"Targeting of lysosomal integral membrane protein LIMP II. 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