{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T05:00:48Z","timestamp":1761541248750,"version":"3.37.3"},"reference-count":35,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2015,3,24]],"date-time":"2015-03-24T00:00:00Z","timestamp":1427155200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100005674","name":"Cystinosis Research Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100005674","id-type":"DOI","asserted-by":"crossref"}]},{"name":"EU 7th Framework Program","award":["EUNEFRON, GA#201590"],"award-info":[{"award-number":["EUNEFRON, GA#201590"]}]},{"DOI":"10.13039\/501100001677","name":"Inserm","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001677","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Traffic"],"published-print":{"date-parts":[[2015,7]]},"abstract":"<jats:p>Cystinosin is a lysosomal cystine transporter defective in cystinosis, an autosomal recessive lysosomal storage disorder. It is composed of seven transmembrane (<jats:styled-content style=\"fixed-case\">TM<\/jats:styled-content>) domains and contains two lysosomal targeting motifs: a tyrosine\u2010based signal (<jats:styled-content style=\"fixed-case\">GYDQL<\/jats:styled-content>) in its C\u2010terminal tail and a non\u2010classical motif in its fifth inter\u2010<jats:styled-content style=\"fixed-case\">TM<\/jats:styled-content> loop. Using the yeast two\u2010hybrid system, we showed that the <jats:styled-content style=\"fixed-case\">GYDQL<\/jats:styled-content> motif specifically interacted with the \u03bc subunit of the adaptor protein complex 3 (<jats:styled-content style=\"fixed-case\">AP<\/jats:styled-content>\u20103). Moreover, cell surface biotinylation and total internal reflection fluorescence microscopy revealed that cystinosin was partially mislocalized to the plasma membrane (<jats:styled-content style=\"fixed-case\">PM<\/jats:styled-content>) in <jats:styled-content style=\"fixed-case\">AP<\/jats:styled-content>\u20103\u2010depleted cells. We generated a chimeric <jats:styled-content style=\"fixed-case\">CD63<\/jats:styled-content> protein to specifically analyze the function of the <jats:styled-content style=\"fixed-case\">GYDQL<\/jats:styled-content> motif. This chimeric protein was targeted to lysosomes in a manner similar to cystinosin and was partially mislocalized to the <jats:styled-content style=\"fixed-case\">PM<\/jats:styled-content> in <jats:styled-content style=\"fixed-case\">AP<\/jats:styled-content>\u20103 knockdown cells where it also accumulated in the <jats:italic>trans<\/jats:italic>\u2010Golgi network and early endosomes. Together with the fact that the surface levels of cystinosin and of the <jats:styled-content style=\"fixed-case\">CD63\u2010GYDQL<\/jats:styled-content> chimeric protein were not increased when clathrin\u2010mediated endocytosis was impaired, our data show that the tyrosine\u2010based motif of cystinosin is a \u2018strong\u2019 <jats:styled-content style=\"fixed-case\">AP<\/jats:styled-content>\u20103 interacting motif responsible for lysosomal targeting of cystinosin by a direct intracellular pathway.<\/jats:p><jats:p><jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"graphic\/tra12277-gra-0001.png\" xlink:title=\"image\"\/><\/jats:p>","DOI":"10.1111\/tra.12277","type":"journal-article","created":{"date-parts":[[2015,3,6]],"date-time":"2015-03-06T07:26:03Z","timestamp":1425626763000},"page":"712-726","source":"Crossref","is-referenced-by-count":9,"title":["Lysosomal Targeting of Cystinosin Requires 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