CLN8 is an endoplasmic reticulum cargo receptor that regulates lysosome biogenesis

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dc.citation.firstpage1370
dc.citation.journalTitleNature Cell Biology
dc.citation.lastpage1377
dc.citation.volumeNumber20
dc.contributor.authordi Ronza, Alberto
dc.contributor.authorBajaj, Lakshya
dc.contributor.authorSharma, Jaiprakash
dc.contributor.authorSanagasetti, Deepthi
dc.contributor.authorLotfi, Parisa
dc.contributor.authorAdamski, Carolyn Joy
dc.contributor.authorCollette, John
dc.contributor.authorPalmieri, Michela
dc.contributor.authorAmawi, Abdallah
dc.contributor.authorPopp, Lauren
dc.contributor.authorChang, Kevin Tommy
dc.contributor.authorMeschini, Maria Chiara
dc.contributor.authorLeung, Hon-Chiu Eastwood
dc.contributor.authorSegatori, Laura
dc.contributor.authorSimonati, Alessandro
dc.contributor.authorSifers, Richard Norman
dc.contributor.authorSantorelli, Filippo Maria
dc.contributor.authorSardiello, Marco
dc.date.accessioned2019-11-22T16:19:56Z
dc.date.available2019-11-22T16:19:56Z
dc.date.issued2018
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.
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.
dc.identifier.digitalnihms-1508962
dc.identifier.doihttps://doi.org/10.1038/s41556-018-0228-7
dc.identifier.urihttps://hdl.handle.net/1911/107718
dc.language.isoeng
dc.publisherSpringer Nature
dc.rightsThis is an author's peer-reviewed final manuscript, as accepted by the publisher. The published article is copyrighted by Springer Nature
dc.titleCLN8 is an endoplasmic reticulum cargo receptor that regulates lysosome biogenesis
dc.typeJournal article
dc.type.dcmiText
dc.type.publicationpost-print
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