ArticleHuman molecular genetics2009
Lowe syndrome patient fibroblasts display Ocrl1-specific cell migration defects that cannot be rescued by the homologous Inpp5b phosphatase.
Article in Human molecular genetics, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
29 citing papers in PubMed, 51 citations in OpenAlex.
- OCRL1 Deficiency Affects the Intracellular Traffic of ApoER2 and Impairs Reelin-Induced Responses.Biomolecules · 2024Article
- Heterogeneity in Lowe Syndrome: Mutations Affecting the Phosphatase Domain of OCRL1 Differ in Impact on Enzymatic Activity and Severity of Cellular Phenotypes.Biomolecules · 2023Article
- Genotype & phenotype in Lowe Syndrome: specific OCRL1 patient mutations differentially impact cellular phenotypes.Human molecular genetics · 2021Article
- Lowe syndrome patient cells display mTOR- and RhoGTPase-dependent phenotypes alleviated by rapamycin and statins.Human molecular genetics · 2020Article
- Effects of Proximal Tubule Shortening on Protein Excretion in a Lowe Syndrome Model.Journal of the American Society of Nephrology : JASN · 2020Article
- Loss of OCRL increases ciliary PI(4,5)PJournal of cell science · 2017Article
- The 5-phosphatase OCRL in Lowe syndrome and Dent disease 2.Nature reviews. Nephrology · 2017Review
- The oculocerebrorenal syndrome of Lowe: an update.Pediatric nephrology (Berlin, Germany) · 2016Review
- OCRL1 engages with the F-BAR protein pacsin 2 to promote biogenesis of membrane-trafficking intermediates.Molecular biology of the cell · 2016Article
- Sac2/INPP5F is an inositol 4-phosphatase that functions in the endocytic pathway.The Journal of cell biology · 2015Article
- The Lowe syndrome protein OCRL1 is required for endocytosis in the zebrafish pronephric tubule.PLoS genetics · 2015Article
- Ciliopathies: the trafficking connection.Traffic (Copenhagen, Denmark) · 2014Review
- The cellular and physiological functions of the Lowe syndrome protein OCRL1.Traffic (Copenhagen, Denmark) · 2014Review
- RhoGTPase-binding proteins, the exocyst complex and polarized vesicle trafficking.Small GTPases · 2014Review
- Compensatory Role of Inositol 5-Phosphatase INPP5B to OCRL in Primary Cilia Formation in Oculocerebrorenal Syndrome of Lowe.PloS one · 2013Article
- The 5-phosphatase OCRL mediates retrograde transport of the mannose 6-phosphate receptor by regulating a Rac1-cofilin signalling module.Human molecular genetics · 2012Article
- Lowe syndrome: Between primary cilia assembly and Rac1-mediated membrane remodeling.Communicative & integrative biology · 2012Article
- OCRL1 modulates cilia length in renal epithelial cells.Traffic (Copenhagen, Denmark) · 2012Article
- Fibronectin attachment protein from bacillus Calmette-Guerin as targeting agent for bladder tumor cells.International journal of cancer · 2012Article
- OCRL localizes to the primary cilium: a new role for cilia in Lowe syndrome.Human molecular genetics · 2012Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The Lowe syndrome (LS) is a life-threatening, developmental disease characterized by mental retardation, cataracts and renal failure. Although this human illness has been linked to defective function of the phosphatidylinositol 5-phosphatase, Ocrl1 (Oculo-Cerebro-Renal syndrome of Lowe protein 1), the mechanism by which this enzyme deficiency triggers the disease is not clear. Ocrl1 is known to localize mainly to the Golgi apparatus and endosomes, however it translocates to plasma membrane ruffles upon cell stimulation with growth factors. The functional implications of this inducible translocation to the plasma membrane are presently unknown. Here we show that Ocrl1 is required for proper cell migration, spreading and fluid-phase uptake in both established cell lines and human dermal fibroblasts. We found that primary fibroblasts from two patients diagnosed with LS displayed defects in these cellular processes. Importantly, these abnormalities were suppressed by expressing wild-type Ocrl1 but not by a phosphatase-deficient mutant. Interestingly, the homologous human PI-5-phosphatase, Inpp5b, was unable to complement the Ocrl1-dependent cell migration defect. Further, Ocrl1 variants that cannot bind the endocytic adaptor AP2 or clathrin, like Inpp5b, were less apt to rescue the migration phenotype. However, no defect in membrane recruitment of AP2/clathrin or in transferrin endocytosis by patient cells was detected. Collectively, our results suggest that Ocrl1, but not Inpp5b, is involved in ruffle-mediated membrane remodeling. Our results provide new elements for understanding how Ocrl1 deficiency leads to the abnormalities associated with the LS.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.