CLN8 is an endoplasmic reticulum cargo receptor that regulates lysosome biogenesis

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dc.citation.firstpage1370en_US
dc.citation.journalTitleNature Cell Biologyen_US
dc.citation.lastpage1377en_US
dc.citation.volumeNumber20en_US
dc.contributor.authordi Ronza, Albertoen_US
dc.contributor.authorBajaj, Lakshyaen_US
dc.contributor.authorSharma, Jaiprakashen_US
dc.contributor.authorSanagasetti, Deepthien_US
dc.contributor.authorLotfi, Parisaen_US
dc.contributor.authorAdamski, Carolyn Joyen_US
dc.contributor.authorCollette, Johnen_US
dc.contributor.authorPalmieri, Michelaen_US
dc.contributor.authorAmawi, Abdallahen_US
dc.contributor.authorPopp, Laurenen_US
dc.contributor.authorChang, Kevin Tommyen_US
dc.contributor.authorMeschini, Maria Chiaraen_US
dc.contributor.authorLeung, Hon-Chiu Eastwooden_US
dc.contributor.authorSegatori, Lauraen_US
dc.contributor.authorSimonati, Alessandroen_US
dc.contributor.authorSifers, Richard Normanen_US
dc.contributor.authorSantorelli, Filippo Mariaen_US
dc.contributor.authorSardiello, Marcoen_US
dc.date.accessioned2019-11-22T16:19:56Zen_US
dc.date.available2019-11-22T16:19:56Zen_US
dc.date.issued2018en_US
dc.description.abstractOrganelle biogenesis requires proper transport of proteins from their site of synthesis to their target subcellular compartment1,2,3. Lysosomal enzymes are synthesized in the endoplasmic reticulum (ER) and traffic through the Golgi complex before being transferred to the endolysosomal system4,5,6, but how they are transferred from the ER to the Golgi is unknown. Here, we show that ER-to-Golgi transfer of lysosomal enzymes requires CLN8, an ER-associated membrane protein whose loss of function leads to the lysosomal storage disorder, neuronal ceroid lipofuscinosis 8 (a type of Batten disease)7. ER-to-Golgi trafficking of CLN8 requires interaction with the COPII and COPI machineries via specific export and retrieval signals localized in the cytosolic carboxy terminus of CLN8. CLN8 deficiency leads to depletion of soluble enzymes in the lysosome, thus impairing lysosome biogenesis. Binding to lysosomal enzymes requires the second luminal loop of CLN8 and is abolished by some disease-causing mutations within this region. Our data establish an unanticipated example of an ER receptor serving the biogenesis of an organelle and indicate that impaired transport of lysosomal enzymes underlies Batten disease caused by mutations in CLN8.en_US
dc.identifier.citationdi Ronza, Alberto, Bajaj, Lakshya, Sharma, Jaiprakash, et al.. "CLN8 is an endoplasmic reticulum cargo receptor that regulates lysosome biogenesis." <i>Nature Cell Biology,</i> 20, (2018) Springer Nature: 1370-1377. https://doi.org/10.1038/s41556-018-0228-7.en_US
dc.identifier.digitalnihms-1508962en_US
dc.identifier.doihttps://doi.org/10.1038/s41556-018-0228-7en_US
dc.identifier.urihttps://hdl.handle.net/1911/107718en_US
dc.language.isoengen_US
dc.publisherSpringer Natureen_US
dc.rightsThis is an author's peer-reviewed final manuscript, as accepted by the publisher. The published article is copyrighted by Springer Natureen_US
dc.titleCLN8 is an endoplasmic reticulum cargo receptor that regulates lysosome biogenesisen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpost-printen_US
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