OCRL controls trafficking through early endosomes via PtdIns4,5P<sub>2</sub>-dependent regulation of endosomal actin

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dc.contributor.authorVicinanza, Mariella
dc.contributor.authorDi Campli, Antonella
dc.contributor.authorPolishchuk, Elena
dc.contributor.authorSantoro, Michele
dc.contributor.authorDi Tullio, Giuseppe
dc.contributor.authorGodi, Anna
dc.contributor.authorLevtchenko, Elena
dc.contributor.authorDe Leo, Maria Giovanna
dc.contributor.authorPolishchuk, Roman
dc.contributor.authorSandoval, Lisette
dc.contributor.authorMarzolo, Maria-Paz
dc.contributor.authorDe Matteis, Maria Antonietta
dc.date.accessioned2025-01-20T23:59:36Z
dc.date.available2025-01-20T23:59:36Z
dc.date.issued2011
dc.description.abstractMutations in the phosphatidylinositol 4,5-bisphosphate (PtdIns4,5P(2)) 5-phosphatase OCRL cause Lowe syndrome, which is characterised by congenital cataracts, central hypotonia, and renal proximal tubular dysfunction. Previous studies have shown that OCRL interacts with components of the endosomal machinery; however, its role in endocytosis, and thus the pathogenic mechanisms of Lowe syndrome, have remained elusive. Here, we show that via its 5-phosphatase activity, OCRL controls early endosome (EE) function. OCRL depletion impairs the recycling of multiple classes of receptors, including megalin (which mediates protein reabsorption in the kidney) that are retained in engorged EEs. These trafficking defects are caused by ectopic accumulation of PtdIns4,5P2 in EEs, which in turn induces an N-WASP-dependent increase in endosomal F-actin. Our data provide a molecular explanation for renal proximal tubular dysfunction in Lowe syndrome and highlight that tight control of PtdIns4,5P2 and F-actin at the EEs is essential for exporting cargoes that transit this compartment. The EMBO Journal (2011) 30, 4970-4985. doi: 10.1038/emboj.2011.354; Published online 4 October 2011
dc.fuente.origenWOS
dc.identifier.doi10.1038/emboj.2011.354
dc.identifier.eissn1460-2075
dc.identifier.issn0261-4189
dc.identifier.urihttps://doi.org/10.1038/emboj.2011.354
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/95300
dc.identifier.wosidWOS:000298368900014
dc.issue.numero24
dc.language.isoen
dc.pagina.final4985
dc.pagina.inicio4970
dc.revistaEmbo journal
dc.rightsacceso restringido
dc.subjectactin
dc.subjectearly endosomes
dc.subjectLowe syndrome
dc.subjectmegalin
dc.subjectphosphoinositides
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleOCRL controls trafficking through early endosomes via PtdIns4,5P<sub>2</sub>-dependent regulation of endosomal actin
dc.typeartículo
dc.volumen30
sipa.indexWOS
sipa.trazabilidadWOS;2025-01-12
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