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{"title"=>"Compensatory Role of Inositol 5-Phosphatase INPP5B to OCRL in Primary Cilia Formation in Oculocerebrorenal Syndrome of Lowe", "type"=>"journal", "authors"=>[{"first_name"=>"Na", "last_name"=>"Luo", "scopus_author_id"=>"55326534400"}, {"first_name"=>"Akhilesh", "last_name"=>"Kumar", "scopus_author_id"=>"57192659434"}, {"first_name"=>"Michael", "last_name"=>"Conwell", "scopus_author_id"=>"55771266600"}, {"first_name"=>"Robert N.", "last_name"=>"Weinreb", "scopus_author_id"=>"35380128600"}, {"first_name"=>"Ryan", "last_name"=>"Anderson", "scopus_author_id"=>"57199165682"}, {"first_name"=>"Yang", "last_name"=>"Sun", "scopus_author_id"=>"7408371207"}], "year"=>2013, "source"=>"PLoS ONE", "identifiers"=>{"pui"=>"369158120", "doi"=>"10.1371/journal.pone.0066727", "scopus"=>"2-s2.0-84879258785", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "pmid"=>"23805271", "sgr"=>"84879258785", "issn"=>"19326203"}, "id"=>"2ae19e55-ee01-3968-bb6b-fbac66987632", "abstract"=>"Inositol phosphatases are important regulators of cell signaling, polarity, and vesicular trafficking. Mutations in OCRL, an inositol polyphosphate 5-phosphatase, result in Oculocerebrorenal syndrome of Lowe, an X-linked recessive disorder that presents with congenital cataracts, glaucoma, renal dysfunction and mental retardation. INPP5B is a paralog of OCRL and shares similar structural domains. The roles of OCRL and INPP5B in the development of cataracts and glaucoma are not understood. Using ocular tissues, this study finds low levels of INPP5B present in human trabecular meshwork but high levels in murine trabecular meshwork. In contrast, OCRL is localized in the trabecular meshwork and Schlemm's canal endothelial cells in both human and murine eyes. In cultured human retinal pigmented epithelial cells, INPP5B was observed in the primary cilia. A functional role for INPP5B is revealed by defects in cilia formation in cells with silenced expression of INPP5B. This is further supported by the defective cilia formation in zebrafish Kupffer's vesicles and in cilia-dependent melanosome transport assays in inpp5b morphants. Taken together, this study indicates that OCRL and INPP5B are differentially expressed in the human and murine eyes, and play compensatory roles in cilia development.", "link"=>"http://www.mendeley.com/research/compensatory-role-inositol-5phosphatase-inpp5b-ocrl-primary-cilia-formation-oculocerebrorenal-syndro", "reader_count"=>30, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Librarian"=>1, "Researcher"=>11, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>4, "Student > Master"=>3, "Other"=>1, "Student > Bachelor"=>5, "Professor"=>1, "Student > Postgraduate"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Librarian"=>1, "Researcher"=>11, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>4, "Student > Master"=>3, "Other"=>1, "Student > Bachelor"=>5, "Professor"=>1, "Student > Postgraduate"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Biochemistry, Genetics and Molecular Biology"=>4, "Agricultural and Biological Sciences"=>18, "Medicine and Dentistry"=>3, "Design"=>1, "Neuroscience"=>1, "Psychology"=>1, "Social Sciences"=>1}, "reader_count_by_subdiscipline"=>{"Design"=>{"Design"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>3}, "Neuroscience"=>{"Neuroscience"=>1}, "Social Sciences"=>{"Social Sciences"=>1}, "Psychology"=>{"Psychology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>18}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>4}, "Unspecified"=>{"Unspecified"=>1}}, "reader_count_by_country"=>{"South Korea"=>2, "Germany"=>1, "Spain"=>1}, "group_count"=>1}

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• http://doi.org/10.1242/dmm.038174
• http://doi.org/10.1038/s41598-019-57066-7
• http://doi.org/10.1042/BCJ20200277
• http://doi.org/10.1038/onc.2017.208
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• http://doi.org/10.1038/ncomms10777
• http://doi.org/10.1016/j.ceb.2018.01.008
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• http://doi.org/10.1073/pnas.1323292111
• http://doi.org/10.1038/nrneph.2017.83
• http://doi.org/10.1681/ASN.2019020125
• http://doi.org/10.4161/cam.27599
• http://doi.org/10.1042/BJ20140361
• http://doi.org/10.1111/tra.12160
• http://doi.org/10.1016/j.devcel.2015.08.001
• http://doi.org/10.3390/jcm8070921
• http://doi.org/10.1371/journal.pgen.1007052
• http://doi.org/10.1002/humu.23139
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• http://doi.org/10.15252/embj.201488044
• http://doi.org/10.1242/jcs.200857

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• {"id"=>"352180840496775168", "text"=>"Compensatory Role of Inositol 5-Phosphatase INPP5B to OCRL in Primary Cilia Form'n in Oculocerebrorenal Synd. of Lowe http://t.co/XEGsn7cJUV", "created_at"=>"2013-07-02T21:43:50Z", "user"=>"jonmoulton", "user_name"=>"Jon D. Moulton", "user_profile_image"=>"http://a0.twimg.com/profile_images/2994846452/96dbc8f717d6cf289a03db1ba953ba76_normal.jpeg"}

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Figshare

• {"files"=>["https://ndownloader.figshare.com/files/1096688"], "description"=>"<p>(A) INPP5B protein levels in HEK293T cells. <i>GFP-Inpp5b</i> lentivirus was generated in HEK293T cells; both GFP-Inpp5b and endogenous INPP5B were immunoblotted in 40 microgram lysates; beta-actin levels are shown. (B) NHF 558, Lowe 1676, and Lowe 3265 fibroblasts were transduced with control, <i>Inpp5b</i> or <i>Inpp5b ΔCAAX</i> lentivirus, serum-starved for 48-hours, and immunostained with acetylated alpha -tubulin. Quantification of cilia length is shown (n >100 cilia, three independent experiments, unpaired t-test, * p = 0.004, ** p = 0.006). (C) <i>Inpp5b</i> mRNA partly rescued the loss of <i>Ocrl</i>. KV cilia of zebrafish embryos injected with <i>ocrl</i> MO (4 ng) with <i>Inpp5b</i> WT mRNA (500 ng) and <i>ocrl</i> MO (4 ng) with <i>Inpp5bΔCAAX</i> mRNA (500 ng) at 6-somite stage were immunostained with acetylated α-tubulin (red), representative images are shown (dash line indicates border of KV). Scale bar 10 micron. (D) Quantification of length of KV cilia in zebrafish embryos injected with <i>ocrl</i> MO (4 ng) with <i>Inpp5b</i> WT mRNA (500 ng) and <i>ocrl</i> MO (4 ng) with <i>Inpp5bΔCAAX</i> mRNA (500 ng). (N >20 embryos, three independent experiments, unpaired t-test, * p = 2.2E-04).</p>", "links"=>[], "tags"=>["Molecular cell biology", "Signal transduction", "Signaling cascades", "Polyphosphoinositide signaling cascade", "Cellular structures", "Anatomy and physiology", "Ocular system", "Ocular anatomy", "Nephrology", "ophthalmology", "Cataracts and other lens disorders", "Inherited eye disorders", "Pediatric ophthalmology", "defect", "ocrl", "cilia"], "article_id"=>727968, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Na Luo", "Akhilesh Kumar", "Michael Conwell", "Robert N. Weinreb", "Ryan Anderson", "Yang Sun"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0066727.g007", "stats"=>{"downloads"=>1, "page_views"=>25, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_INPP5B_can_partly_rescue_the_defect_of_OCRL_in_primary_cilia_development_/727968", "title"=>"INPP5B can partly rescue the defect of OCRL in primary cilia development.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-06-21 01:49:46"}
• {"files"=>["https://ndownloader.figshare.com/files/1096685"], "description"=>"<p>(A) Domain structure of human INPP5B protein. (B) hTERT-RPE1 cells were transduced by <i>GFP-Inpp5b</i> or <i>GFP-Inpp5bΔCAAX</i> lentivirus, starved for 48 hr, and then analyzed by immunostaining with anti-acetylated alpha-tubulin antibody. Scale bar 10 micron. (C) Lengths of primary cilia in <i>Inpp5b</i> and <i>Inpp5b</i>-<i>delta</i>-CAAX cells. hTERT-RPE1 cells were transduced with either <i>GFP-Inpp5b</i> or <i>GFP-Inpp5b</i>-<i>delta</i>-<i>CAAX</i> lentivirus, serum starved for 48 hr, and stained with anti-acetylated alpha-tubulin antibody. Scatter plot showing distribution pattern of ciliary length (3.4±0.4 micron in <i>INPP5B</i> and 2.8±0.3 micron in <i>Inpp5bΔCAAX</i> cells, unpaired t-test, p = 1.36E-06, n >160 cilia, three independent experiments). (D) <i>INPP5BΔCAAX</i> mRNA failed to rescue the loss of <i>inpp5b</i>. KV cilia of zebrafish embryos injected with <i>inpp5b</i> MO (4 ng), <i>inpp5b</i> MO (4 ng) with <i>INPP5B</i> WT mRNA (500 ng) and <i>inpp5b</i> MO (4 ng) with <i>INPP5B ΔCAAX</i> mRNA (500 ng) at 6-somite stage were immunostained with acetylated α-tubulin (red), representative images are shown (dash line indicates border of KV). Scale bar 10 micron. (E–F) Quantification of length (E) and number (F) of KV cilia in zebrafish embryos injected with <i>inpp5b</i> MO (4 ng), <i>inpp5b</i> MO (4 ng) with <i>INPP5B</i> WT mRNA (500 ng) and <i>inpp5b</i> MO (4 ng) with <i>INPP5B ΔCAAX</i> mRNA (500 ng). (N >20 embryos, three independent experiments, unpaired t-test, * p = 3.9E-26 in E and * p = 9E-06 in F).</p>", "links"=>[], "tags"=>["Molecular cell biology", "Signal transduction", "Signaling cascades", "Polyphosphoinositide signaling cascade", "Cellular structures", "Anatomy and physiology", "Ocular system", "Ocular anatomy", "Nephrology", "ophthalmology", "Cataracts and other lens disorders", "Inherited eye disorders", "Pediatric ophthalmology", "inpp5b", "caax", "mutant", "cilia"], "article_id"=>727966, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Na Luo", "Akhilesh Kumar", "Michael Conwell", "Robert N. Weinreb", "Ryan Anderson", "Yang Sun"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0066727.g005", "stats"=>{"downloads"=>1, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effect_of_INPP5B_CAAX_mutant_on_cilia_localization_/727966", "title"=>"Effect of INPP5B CAAX mutant on cilia localization.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-06-21 01:49:46"}
• {"files"=>["https://ndownloader.figshare.com/files/1096681"], "description"=>"<p>(A) hTERT-RPE1 cells were starved for 48 hr, and analyzed by immunostaining with anti-INPP5B antibody and anti-acetylated alpha-tubulin antibody. Scale bar 5 micron. (B) Control and <i>INPP5B</i> shRNA hTERT-RPE1 cells were starved for 48 hr, and analyzed by immunostaining with anti-INPP5B antibody and anti-acetylated alpha-tubulin antibody. Scale bar 5 micron. (C-D) Control and <i>INPP5B</i> shRNA hTERT-RPE1 cells were starved for 24 hr or 48 hr, and analyzed by immunostaining with anti-acetylated alpha-tubulin antibody. Percent ciliated cells (C) and the length of cilia (D) were quantified. (n = the number of cilia n >100 cilia, three independent experiments, unpaired t-test, * p = 2.1E-08 in D, * p = 3.1 E-09 in E; ns, not statistically significant).</p>", "links"=>[], "tags"=>["Molecular cell biology", "Signal transduction", "Signaling cascades", "Polyphosphoinositide signaling cascade", "Cellular structures", "Anatomy and physiology", "Ocular system", "Ocular anatomy", "Nephrology", "ophthalmology", "Cataracts and other lens disorders", "Inherited eye disorders", "Pediatric ophthalmology", "localizes"], "article_id"=>727963, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Na Luo", "Akhilesh Kumar", "Michael Conwell", "Robert N. Weinreb", "Ryan Anderson", "Yang Sun"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0066727.g002", "stats"=>{"downloads"=>0, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_INPP5B_localizes_to_primary_cilia_/727963", "title"=>"INPP5B localizes to primary cilia.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-06-21 01:49:46"}
• {"files"=>["https://ndownloader.figshare.com/files/1096680"], "description"=>"<p>(A) Diagram of trabecular meshwork and Schlemm’s canal endothelial cells (aqueous flow, red; trabecular meshwork, arrow; Schlemm’s canal endothelial cells, arrowhead). (B) Human eye sectioned and stained by H&E or immunofluorescence with anti-OCRL (green) or anti-INPP5B antibody (green), and DAPI (blue). Staining of trabecular meshwork cells in vesicular pattern (insert, arrow) and Schlemm’s canal (arrowhead). Scale bar 10 micron. (C) Lens epithelial cells (arrow) stained with H&E, anti-OCRL antibody (green) or anti-INPP5B antibody (green), and DAPI (blue). Scale bar 10 micron. (D) Ciliary body epithelial (arrowhead) cells stained with H&E, anti-OCRL antibody (green) or anti-INPP5B antibody (green), and DAPI (blue). Scale bar 10 micron. (E) Mouse eye sectioned and stained with H&E, anti-OCRL antibody (green) or anti-INPP5B antibody (green), and DAPI (blue). Staining of trabecular meshwork cells in vesicular pattern (dash line indicates border of trabecular meshwork). Scale bar 10 micron. (F) Immunoblot of <i>INPP5B</i> expression in 30 microgram lysates of hTERT-RPE1 shRNA knockdown cells compared to beta-actin. (G) Immunoblot analysis of 40 microgram lysates of human and mouse trabecular meshwork with anti-OCRL, anti-INPP5B and anti-beta-actin antibodies.</p>", "links"=>[], "tags"=>["Molecular cell biology", "Signal transduction", "Signaling cascades", "Polyphosphoinositide signaling cascade", "Cellular structures", "Anatomy and physiology", "Ocular system", "Ocular anatomy", "Nephrology", "ophthalmology", "Cataracts and other lens disorders", "Inherited eye disorders", "Pediatric ophthalmology", "ocrl", "inpp5b", "ocular"], "article_id"=>727962, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Na Luo", "Akhilesh Kumar", "Michael Conwell", "Robert N. Weinreb", "Ryan Anderson", "Yang Sun"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0066727.g001", "stats"=>{"downloads"=>1, "page_views"=>49, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Localization_of_OCRL_and_INPP5B_in_human_ocular_tissue_/727962", "title"=>"Localization of OCRL and INPP5B in human ocular tissue.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-06-21 01:49:46"}
• {"files"=>["https://ndownloader.figshare.com/files/1096684"], "description"=>"<p>(A) <i>INPP5B</i> WT mRNA rescue the loss of <i>inpp5b</i>. KV cilia of zebrafish embryos injected with control MO (4 ng), <i>inpp5b</i> MO (4 ng) or <i>inpp5b</i> MO (4 ng) and <i>INPP5B</i> WT mRNA (500 ng) at 6-somite stage were immunostained with acetylated α-tubulin (red), representative images are shown (dash line indicates border of KV). Scale bar 10 micron. (B–C) Quantification of number (B) and length (C) of KV cilia in zebrafish embryos injected with control MO (4 ng), <i>inpp5b</i> MO (4 ng) or <i>inpp5b</i> MO (4 ng) and <i>INPP5B</i> WT mRNA (500 ng). (N >20 embryos, three independent experiments, unpaired t-test, * p = 3.4E-03 in B and * p = 1.9E-23 in C). (D) <i>INPP5B</i> WT mRNA rescue of <i>inpp5b</i> pronephric cilia formation. Representative image of pronephric cilia of zebrafish embryos at 24 hpf stage, injected with control MO (4 ng), <i>inpp5b</i> MO (4 ng) or <i>inpp5b</i> MO (4 ng) and <i>INPP5B</i> WT mRNA (500 ng), immunostaining with acetylated α-tubulin (red). Scale bar 10 micron. (E) Pronephric cilia length of control and <i>inpp5b</i> MO. Pronephric cilia of zebrafish embryos injected with control MO (4 ng), <i>inpp5b</i> MO (4 ng) or <i>inpp5b</i> MO (4 ng) and <i>INPP5B</i> WT mRNA (500 ng) at 24 hpf stage were analyzed by immunostaining with acetylated alpha-tubulin and cilia length was measured. (N >200 cilia; three independent experiments, unpaired t-test, * p = 5.45E-18). (F) <i>Ocrl</i> and <i>Inpp5b</i> morphants showed slowed retrograde melanosome transport. Representative photos are shown for the melanosomes in <i>Ocrl</i> and <i>Inpp5b</i> morphants before and after treatment with epinephrine in 5 dpf embryos (box, region of pigment evaluation). (G) Quantification of the response time for epinephrine treatments in the control MO (2 ng), <i>ocrl</i> MO (2 ng), <i>ocrl</i> MO (2 ng) and <i>OCRL</i> WT mRNA (500 pg), <i>inpp5b</i> MO (2 ng), and <i>inpp5b</i> MO (2 ng) and <i>Inpp5b</i> WT mRNA (500 pg) embryos (N >30 embryos, three independent experiments, unpaired t-test, * p = 4.6E-50, ** p = 2.3E-43).</p>", "links"=>[], "tags"=>["Molecular cell biology", "Signal transduction", "Signaling cascades", "Polyphosphoinositide signaling cascade", "Cellular structures", "Anatomy and physiology", "Ocular system", "Ocular anatomy", "Nephrology", "ophthalmology", "Cataracts and other lens disorders", "Inherited eye disorders", "Pediatric ophthalmology", "cilia", "zebrafish"], "article_id"=>727965, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Na Luo", "Akhilesh Kumar", "Michael Conwell", "Robert N. Weinreb", "Ryan Anderson", "Yang Sun"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0066727.g004", "stats"=>{"downloads"=>2, "page_views"=>20, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Defects_of_cilia_formation_in_Inpp5b_zebrafish_morphants_/727965", "title"=>"Defects of cilia formation in <i>Inpp5b</i> zebrafish morphants.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-06-21 01:49:46"}
• {"files"=>["https://ndownloader.figshare.com/files/1096682"], "description"=>"<p>(A) Immunoblot analysis of 40 microgram of total lysates of zebrafish embryo injected with control MO (4 ng) or <i>inpp5b</i> MO (4 ng) at 48 hpf with anti-INPP5B and anti-beta-actin antibodies. (B) Zebrafish embryos were injected with <i>p53</i> MO (2 ng) or <i>p53</i> MO (2 ng) and <i>inpp5b</i> MO (4 ng). Representative phenotypes of microphthalmia (black arrowhead), pericardial edema (small arrow), body axis asymmetry, kinked tail (white arrow), pronephric cyst formation (red arrow), and hypopigmentation were observed at 48 hpf. Scale bar 250 micron. (C) Dose-dependent effect of morpholinos in zebrafish. Control or <i>inpp5b</i> MO at indicated doses was injected into zebrafish embryos, and phenotypes of microphthalmia, kinked tail, and body asymmetry were quantified at 48 hpf (ANOVA, F = 92, p = 3.6E-10), kinked tail (ANOVA, F = 3.6, p = 0.08), and body asymmetry (ANOVA, F = 5.2, p = 0.04). (N = the number of injected embryos N >50). (D) Quantification of eye size of morphants at 24 hpf, 48 hpf and 72 hpf. The eye size was determined by the longest diameters in dorsal view. (N >40 embryos, three independent experiments, unpaired t-test, * p = 4.98E-07 ** p = 2.1E-10, ns, not statistically significant). (E) Cresyl violet staining of ocular sections of zebrafish larvae (5 dpf) injected with control MO (4 ng) or <i>inpp5b</i> MO (4 ng). Scale bar 30 micron. (F) Zebrafish embryos were injected with control MO (4 ng), <i>inpp5b</i> MO (4 ng) or <i>inpp5b</i> MO (4 ng) and <i>Inpp5b</i> WT mRNA (<i>Inpp5b</i> mRNA, 500 pg). Representative phenotypes of microphthalmia (arrowhead), pericardial edema (arrow), body axis asymmetry, kinked tail (white arrow), pronephric cyst formation (red arrow), and hypopigmentation were observed at 48 hpf. Scale bar 250 micron. (G) Quantification of eye size of zebrafish morphants at 24 hpf and 48 hpf. (N >40 embryos, three independent experiments, unpaired t-test, * p = 4.5E-05). (H) The ventral sides of embryos were injected with control MO (4 ng), <i>inpp5b</i> MO (4 ng) or <i>inpp5b</i> MO (4 ng) and <i>Inpp5b</i> WT mRNA (500 pg). Scale bar 100 micron.</p>", "links"=>[], "tags"=>["Molecular cell biology", "Signal transduction", "Signaling cascades", "Polyphosphoinositide signaling cascade", "Cellular structures", "Anatomy and physiology", "Ocular system", "Ocular anatomy", "Nephrology", "ophthalmology", "Cataracts and other lens disorders", "Inherited eye disorders", "Pediatric ophthalmology", "morpholino"], "article_id"=>727964, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Na Luo", "Akhilesh Kumar", "Michael Conwell", "Robert N. Weinreb", "Ryan Anderson", "Yang Sun"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0066727.g003", "stats"=>{"downloads"=>0, "page_views"=>26, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Inpp5b_morpholino_affects_multiple_organ_development_in_zebrafish_/727964", "title"=>"<i>Inpp5b</i> morpholino affects multiple organ development in zebrafish.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-06-21 01:49:46"}
• {"files"=>["https://ndownloader.figshare.com/files/1096689"], "description"=>"<div><p>Inositol phosphatases are important regulators of cell signaling, polarity, and vesicular trafficking. Mutations in <i>OCRL</i>, an inositol polyphosphate 5-phosphatase, result in Oculocerebrorenal syndrome of Lowe, an X-linked recessive disorder that presents with congenital cataracts, glaucoma, renal dysfunction and mental retardation. <i>INPP5B</i> is a paralog of <i>OCRL</i> and shares similar structural domains. The roles of <i>OCRL</i> and <i>INPP5B</i> in the development of cataracts and glaucoma are not understood. Using ocular tissues, this study finds low levels of INPP5B present in human trabecular meshwork but high levels in murine trabecular meshwork. In contrast, OCRL is localized in the trabecular meshwork and Schlemm’s canal endothelial cells in both human and murine eyes. In cultured human retinal pigmented epithelial cells, INPP5B was observed in the primary cilia. A functional role for INPP5B is revealed by defects in cilia formation in cells with silenced expression of <i>INPP5B</i>. This is further supported by the defective cilia formation in zebrafish Kupffer’s vesicles and in cilia-dependent melanosome transport assays in <i>inpp5b</i> morphants. Taken together, this study indicates that <i>OCRL</i> and <i>INPP5B</i> are differentially expressed in the human and murine eyes, and play compensatory roles in cilia development.</p></div>", "links"=>[], "tags"=>["Molecular cell biology", "Signal transduction", "Signaling cascades", "Polyphosphoinositide signaling cascade", "Cellular structures", "Anatomy and physiology", "Ocular system", "Ocular anatomy", "Nephrology", "ophthalmology", "Cataracts and other lens disorders", "Inherited eye disorders", "Pediatric ophthalmology", "inositol", "5-phosphatase", "inpp5b", "ocrl", "cilia", "oculocerebrorenal"], "article_id"=>727969, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Na Luo", "Akhilesh Kumar", "Michael Conwell", "Robert N. Weinreb", "Ryan Anderson", "Yang Sun"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0066727", "stats"=>{"downloads"=>4, "page_views"=>22, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Compensatory_Role_of_Inositol_5_Phosphatase_INPP5B_to_OCRL_in_Primary_Cilia_Formation_in_Oculocerebrorenal_Syndrome_of_Lowe_/727969", "title"=>"Compensatory Role of Inositol 5-Phosphatase INPP5B to OCRL in Primary Cilia Formation in Oculocerebrorenal Syndrome of Lowe", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-06-21 01:49:46"}
• {"files"=>["https://ndownloader.figshare.com/files/1096687"], "description"=>"<p>(A) Representative phenotypes of morphants co-injected with <i>ocrl</i> and <i>inpp5b</i> MO. Scale bar 250 micron. (B) Dose-dependent effect of two morpholinos in zebrafish. Control <i>ocrl</i> and <i>inpp5b</i> MO at indicated doses were injected into zebrafish embryos, and different grades of phenotypes were quantified at 48 hpf (N >250 embryos per group). (C) Transgenic <i>mOcrl^−/−:mInpp5b^−/−:hINPP5B</i>^+/+ mouse eyes were sectioned and stained by H&E, anti-OCRL antibody (green) or anti-INPP5B antibody (green), and DAPI (blue). Staining of trabecular meshwork cells in vesicular pattern (arrow), dash line indicates border of cornea and iris. Scale bar 10 micron. (D) Photoreceptor cells (arrow) from the transgenic mouse eye section stained with H&E, anti-OCRL antibody (green) or anti-INPP5B antibody (green), and DAPI (blue). Scale bar 10 micron. (E) Lens epithelial cells (arrow) stained with H&E, anti-OCRL antibody (green) or anti-INPP5B antibody (green), and DAPI (blue). Scale bar 10 micron.</p>", "links"=>[], "tags"=>["Molecular cell biology", "Signal transduction", "Signaling cascades", "Polyphosphoinositide signaling cascade", "Cellular structures", "Anatomy and physiology", "Ocular system", "Ocular anatomy", "Nephrology", "ophthalmology", "Cataracts and other lens disorders", "Inherited eye disorders", "Pediatric ophthalmology", "ocrl", "synergistically"], "article_id"=>727967, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Na Luo", "Akhilesh Kumar", "Michael Conwell", "Robert N. Weinreb", "Ryan Anderson", "Yang Sun"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0066727.g006", "stats"=>{"downloads"=>0, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_INPP5B_and_OCRL_act_synergistically_in_eye_development_/727967", "title"=>"INPP5B and OCRL act synergistically in eye development.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-06-21 01:49:46"}

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Relative Metric

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F1000Prime