{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nOCRL is a phosphatidylinositol 4,5‐bisphosphate [PI(4,5)P₂] 5‐phosphatase whose enzymatic activity is essential for regulating local phosphoinositide levels that drive membrane dynamics. By hydrolyzing PI(4,5)P₂ at defined cellular locales, OCRL facilitates actin remodeling—a process fundamental to cytokinesis abscission, clathrin‐mediated vesicle uncoating and proper endosomal sorting. In addition, OCRL directly interacts with small GTPases (including Rab35 and Rac) that both target and stimulate its phosphatase activity, thereby ensuring the correct assembly and function of membrane compartments such as the Golgi apparatus and early endosomes."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "22"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its role at the plasma membrane and in cytokinesis, OCRL is pivotal for maintaining endosomal integrity and directing appropriate sorting of cargo. Its activity is critical for recycling receptors—including the mannose 6‐phosphate receptor—as well as for modulating autophagic flux via regulation of lysosomal PI(4,5)P₂ levels. Moreover, OCRL contributes to the formation and function of primary cilia by controlling the composition of phosphoinositides at the ciliary transition zone; defects in this function are increasingly recognized as contributory to the ocular and neurological manifestations observed in Lowe syndrome."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "23", "end_ref": "32"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nOCRL further exerts its effects through interactions with a broad network of trafficking adaptors and small GTPases that link lipid dephosphorylation to membrane remodeling. Its association with clathrin, Rab‐effector proteins (including interactions mediated through IPIP27 and pacsin 2) and modulation of actin dynamics are central to the formation and maturation of transport intermediates. 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"}, {"type": "b", "children": [{"type": "t", "text": "Lowe Syndrome protein OCRL1 supports maturation of polarized epithelial cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0024044"}], "href": "https://doi.org/10.1371/journal.pone.0024044"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21901156"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21901156"}]}, {"type": "r", "ref": 24, "children": [{"type": "t", "text": "Mariella Vicinanza, Antonella Di Campli, Elena Polishchuk, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "The Lowe syndrome protein OCRL1 is involved in primary cilia assembly."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddr615"}], "href": "https://doi.org/10.1093/hmg/ddr615"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22228094"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22228094"}]}, {"type": "r", "ref": 26, "children": [{"type": "t", "text": "Andreas Kühbacher, Daphné Dambournet, Arnaud Echard, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Phosphatidylinositol 5-phosphatase oculocerebrorenal syndrome of Lowe protein (OCRL) controls actin dynamics during early steps of Listeria monocytogenes infection."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M111.315788"}], "href": "https://doi.org/10.1074/jbc.M111.315788"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22351770"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22351770"}]}, {"type": "r", "ref": 27, "children": [{"type": "t", "text": "Guojin Wu, Wei Zhang, Tao Na, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Suppression of intestinal calcium entry channel TRPV6 by OCRL, a lipid phosphatase associated with Lowe syndrome and Dent disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Cell Physiol (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajpcell.00277.2011"}], "href": "https://doi.org/10.1152/ajpcell.00277.2011"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22378746"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22378746"}]}, {"type": "r", "ref": 28, "children": [{"type": "t", "text": "Na Luo, Callah C West, Carlos A Murga-Zamalloa, et al. "}, {"type": "b", "children": [{"type": "t", "text": "OCRL localizes to the primary cilium: a new role for cilia in Lowe syndrome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/dds163"}], "href": "https://doi.org/10.1093/hmg/dds163"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22543976"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22543976"}]}, {"type": "r", "ref": 29, "children": [{"type": "t", "text": "Nina Hagemann, Xiaomin Hou, Roger S Goody, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Crystal structure of the Rab binding domain of OCRL1 in complex with Rab8 and functional implications of the OCRL1/Rab8 module for Lowe syndrome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Small GTPases (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4161/sgtp.19380"}], "href": "https://doi.org/10.4161/sgtp.19380"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22790198"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22790198"}]}, {"type": "r", "ref": 30, "children": [{"type": "t", "text": "Vanessa A van Rahden, Kristina Brand, Juliane Najm, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The 5-phosphatase OCRL mediates retrograde transport of the mannose 6-phosphate receptor by regulating a Rac1-cofilin signalling module."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/dds343"}], "href": "https://doi.org/10.1093/hmg/dds343"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22907655"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22907655"}]}, {"type": "r", "ref": 31, "children": [{"type": "t", "text": "Sabrina Marion, Julie Mazzolini, Floriane Herit, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The NF-κB signaling protein Bcl10 regulates actin dynamics by controlling AP1 and OCRL-bearing vesicles."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Dev Cell (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.devcel.2012.09.021"}], "href": "https://doi.org/10.1016/j.devcel.2012.09.021"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23153494"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23153494"}]}, {"type": "r", "ref": 32, "children": [{"type": "t", "text": "Takashi Sekine, Fusako Komoda, Kenichiro Miura, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Japanese Dent disease has a wider clinical spectrum than Dent disease in Europe/USA: genetic and clinical studies of 86 unrelated patients with low-molecular-weight proteinuria."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nephrol Dial Transplant (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/ndt/gft394"}], "href": "https://doi.org/10.1093/ndt/gft394"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24081861"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24081861"}]}, {"type": "r", "ref": 33, "children": [{"type": "t", "text": "Lionel Trésaugues, Camilla Silvander, Susanne Flodin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Structural basis for phosphoinositide substrate recognition, catalysis, and membrane interactions in human inositol polyphosphate 5-phosphatases."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Structure (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.str.2014.01.013"}], "href": "https://doi.org/10.1016/j.str.2014.01.013"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24704254"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24704254"}]}, {"type": "r", "ref": 34, "children": [{"type": "t", "text": "Ramiro Nández, Daniel M Balkin, Mirko Messa, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A role of OCRL in clathrin-coated pit dynamics and uncoating revealed by studies of Lowe syndrome cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Elife (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.7554/eLife.02975"}], "href": "https://doi.org/10.7554/eLife.02975"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25107275"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25107275"}]}, {"type": "r", "ref": 35, "children": [{"type": "t", "text": "Na Luo, Michael D Conwell, Xingjuan Chen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Primary cilia signaling mediates intraocular pressure sensation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1323292111"}], "href": "https://doi.org/10.1073/pnas.1323292111"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25143588"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25143588"}]}, {"type": "r", "ref": 36, "children": [{"type": "t", "text": "Rodrick Montjean, Rifdat Aoidi, Pierrette Desbois, et al. "}, {"type": "b", "children": [{"type": "t", "text": "OCRL-mutated fibroblasts from patients with Dent-2 disease exhibit INPP5B-independent phenotypic variability relatively to Lowe syndrome cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddu514"}], "href": "https://doi.org/10.1093/hmg/ddu514"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25305077"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25305077"}]}, {"type": "r", "ref": 37, "children": [{"type": "t", "text": "Peter G Billcliff, Christopher J Noakes, Zenobia B Mehta, et al. "}, {"type": "b", "children": [{"type": "t", "text": "OCRL1 engages with the F-BAR protein pacsin 2 to promote biogenesis of membrane-trafficking intermediates."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Biol Cell (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1091/mbc.E15-06-0329"}], "href": "https://doi.org/10.1091/mbc.E15-06-0329"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26510499"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26510499"}]}, {"type": "r", "ref": 38, "children": [{"type": "t", "text": "Clothilde Cauvin, Morgane Rosendale, Neetu Gupta-Rossi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Rab35 GTPase Triggers Switch-like Recruitment of the Lowe Syndrome Lipid Phosphatase OCRL on Newborn Endosomes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Curr Biol (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cub.2015.11.040"}], "href": "https://doi.org/10.1016/j.cub.2015.11.040"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26725203"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26725203"}]}, {"type": "r", "ref": 39, "children": [{"type": "t", "text": "Maria Giovanna De Leo, Leopoldo Staiano, Mariella Vicinanza, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Autophagosome-lysosome fusion triggers a lysosomal response mediated by TLR9 and controlled by OCRL."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Cell Biol (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncb3386"}], "href": "https://doi.org/10.1038/ncb3386"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27398910"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27398910"}]}, {"type": "r", "ref": 40, "children": [{"type": "t", "text": "Marcin Zaniew, Arend Bökenkamp, Marcin Kolbuc, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Long-term renal outcome in children with OCRL mutations: retrospective analysis of a large international cohort."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nephrol Dial Transplant (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/ndt/gfw350"}], "href": "https://doi.org/10.1093/ndt/gfw350"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27708066"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27708066"}]}, {"type": "r", "ref": 41, "children": [{"type": "t", "text": "Maria Antonietta De Matteis, Leopoldo Staiano, Francesco Emma, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The 5-phosphatase OCRL in Lowe syndrome and Dent disease 2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Rev Nephrol (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nrneph.2017.83"}], "href": "https://doi.org/10.1038/nrneph.2017.83"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28669993"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28669993"}]}, {"type": "r", "ref": 42, "children": [{"type": "t", "text": "Philipp P Prosseda, Na Luo, Biao Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Loss of OCRL increases ciliary PI(4,5)P"}, {"type": "a", "children": [{"type": "t", "text": "sub"}], "href": "sub"}, {"type": "t", "text": "2"}, {"type": "a", "children": [{"type": "t", "text": "/sub"}], "href": "/sub"}, {"type": "t", "text": " in Lowe oculocerebrorenal syndrome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Sci (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1242/jcs.200857"}], "href": "https://doi.org/10.1242/jcs.200857"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28871046"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28871046"}]}, {"type": "r", "ref": 43, "children": [{"type": "t", "text": "Qing Ye, Qian Shen, Jia Rao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Multicenter study of the clinical features and mutation gene spectrum of Chinese children with Dent disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Genet (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/cge.13663"}], "href": "https://doi.org/10.1111/cge.13663"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31674016"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31674016"}]}, {"type": "r", "ref": 44, "children": [{"type": "t", "text": "Biao Wang, Wei He, Philipp P Prosseda, et al. "}, {"type": "b", "children": [{"type": "t", "text": "OCRL regulates lysosome positioning and mTORC1 activity through SSX2IP-mediated microtubule anchoring."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EMBO Rep (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.15252/embr.202052173"}], "href": "https://doi.org/10.15252/embr.202052173"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33987909"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33987909"}]}, {"type": "r", "ref": 45, "children": [{"type": "t", "text": "Won Young Choi, Seongok Kim, Philipp Aurass, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SdhA blocks disruption of the Legionella-containing vacuole by hijacking the OCRL phosphatase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Rep (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.celrep.2021.109894"}], "href": "https://doi.org/10.1016/j.celrep.2021.109894"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34731604"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34731604"}]}]}]}