Crag Is a GEF for Rab11 Required for Rhodopsin Trafficking and Maintenance of Adult Photoreceptor Cells
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{"title"=>"Crag Is a GEF for Rab11 Required for Rhodopsin Trafficking and Maintenance of Adult Photoreceptor Cells", "type"=>"journal", "authors"=>[{"first_name"=>"Bo", "last_name"=>"Xiong", "scopus_author_id"=>"55504148000"}, {"first_name"=>"Vafa", "last_name"=>"Bayat", "scopus_author_id"=>"8668838900"}, {"first_name"=>"Manish", "last_name"=>"Jaiswal", "scopus_author_id"=>"12800827600"}, {"first_name"=>"Ke", "last_name"=>"Zhang", "scopus_author_id"=>"55505028300"}, {"first_name"=>"Hector", "last_name"=>"Sandoval", "scopus_author_id"=>"15052281000"}, {"first_name"=>"Wu Lin", "last_name"=>"Charng", "scopus_author_id"=>"36459546900"}, {"first_name"=>"Tongchao", "last_name"=>"Li", "scopus_author_id"=>"55540645400"}, {"first_name"=>"Gabriela", "last_name"=>"David", "scopus_author_id"=>"14014529400"}, {"first_name"=>"Lita", "last_name"=>"Duraine", "scopus_author_id"=>"55453311300"}, {"first_name"=>"Yong Qi", "last_name"=>"Lin", "scopus_author_id"=>"24338249300"}, {"first_name"=>"G. Gregory", "last_name"=>"Neely", "scopus_author_id"=>"22941514000"}, {"first_name"=>"Shinya", "last_name"=>"Yamamoto", "scopus_author_id"=>"55475460900"}, {"first_name"=>"Hugo J.", "last_name"=>"Bellen", "scopus_author_id"=>"7005166130"}], "year"=>2012, "source"=>"PLoS Biology", "identifiers"=>{"pmid"=>"23226104", "doi"=>"10.1371/journal.pbio.1001438", "sgr"=>"84871691612", "isbn"=>"1545-7885 (Electronic)\\n1544-9173 (Linking)", "scopus"=>"2-s2.0-84871691612", "issn"=>"15449173", "pui"=>"368012948"}, "id"=>"52b88fd6-ed30-316b-9a94-4ba56d899258", "abstract"=>"Rhodopsins (Rhs) are light sensors, and Rh1 is the major Rh in the Drosophila photoreceptor rhabdomere membrane. Upon photoactivation, a fraction of Rh1 is internalized and degraded, but it remains unclear how the rhabdomeric Rh1 pool is replenished and what molecular players are involved. Here, we show that Crag, a DENN protein, is a guanine nucleotide exchange factor for Rab11 that is required for the homeostasis of Rh1 upon light exposure. The absence of Crag causes a light-induced accumulation of cytoplasmic Rh1, and loss of Crag or Rab11 leads to a similar photoreceptor degeneration in adult flies. Furthermore, the defects associated with loss of Crag can be partially rescued with a constitutive active form of Rab11. We propose that upon light stimulation, Crag is required for trafficking of Rh from the trans-Golgi network to rhabdomere membranes via a Rab11-dependent vesicular transport.", "link"=>"http://www.mendeley.com/research/crag-gef-rab11-required-rhodopsin-trafficking-maintenance-adult-photoreceptor-cells", "reader_count"=>80, "reader_count_by_academic_status"=>{"Unspecified"=>3, "Professor > Associate Professor"=>7, "Researcher"=>19, "Student > Doctoral Student"=>7, "Student > Ph. D. Student"=>19, "Student > Postgraduate"=>1, "Student > Master"=>8, "Other"=>2, "Student > Bachelor"=>12, "Lecturer"=>1, "Lecturer > Senior Lecturer"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>3, "Professor > Associate Professor"=>7, "Researcher"=>19, "Student > Doctoral Student"=>7, "Student > Ph. D. Student"=>19, "Student > Postgraduate"=>1, "Student > Master"=>8, "Other"=>2, "Student > Bachelor"=>12, "Lecturer"=>1, "Lecturer > Senior Lecturer"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>5, "Biochemistry, Genetics and Molecular Biology"=>8, "Agricultural and Biological Sciences"=>54, "Medicine and Dentistry"=>6, "Neuroscience"=>4, "Physics and Astronomy"=>1, "Social Sciences"=>1, "Immunology and Microbiology"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>6}, "Neuroscience"=>{"Neuroscience"=>4}, "Social Sciences"=>{"Social Sciences"=>1}, "Physics and Astronomy"=>{"Physics and Astronomy"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>54}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>8}, "Unspecified"=>{"Unspecified"=>5}}, "reader_count_by_country"=>{"Turkey"=>1, "Belgium"=>1, "United States"=>1, "Japan"=>1, "Brazil"=>1, "Peru"=>1, "Germany"=>1, "India"=>1, "Spain"=>1}, "group_count"=>1}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/531689"], "description"=>"<p>(A) In adult flies, blue light triggers the conformational change of Rh to metaRh, whereas orange light is required for converting metaRh to Rh. In the presence of blue light and absence of orange light, metaRh is accumulated in the rhabdomere, which in turn triggers massive endocytosis and degradation of Rh. (B) Fly heads with control or <i>Crag<sup>C</sup></i> mutant clones in the eyes were collected from flies that were kept in the dark or in blue light for 6 h with or without 24 h of recovery. Western blots and dot blots were performed to detect total Rh1 and Actin (loading control) levels. Note that in both genotypes, the Rh1 level significantly decreased after 6 h of blue light treatment and was restored after 24 h of recovery in the dark. (C) Whole mount staining of Rh1 in photoreceptors kept in the dark, exposed to 6 h of blue light, or exposed to 6 h blue light with 18 or 36 h of recovery in the dark. 6 h of blue light treatment triggers massive endocytosis of Rh1 in both control and <i>Crag</i> mutant photoreceptors. Note the strong Rh1 staining in the cytosol. After 18 h of recovery, a crescent shaped pattern of Rh1 is reformed in controls but not in <i>Crag</i> mutant photoreceptors. Rh1 accumulation is persistent in <i>Crag</i> mutant cells after 36 h of recovery. Note that breakdown of rhabdomeres (indicated by red arrows) is observed in flies kept for 36 h in the dark but not in flies kept for 18 h in the dark after blue light exposure. Scale bar, 5 µM. (D) Immunostaining of the trans-Golgi compartment (Peanut agglutinin) and Rh1 in flies after 6 h of blue light exposure and 18 h of dark recovery. Note the enlargement of the trans-Golgi compartment and the colocalization between Rh1 and the trans-Golgi compartment (indicated by white arrowheads) in <i>Crag</i> mutant cells.</p>", "links"=>[], "tags"=>["rh1", "rhabdomeres"], "article_id"=>202170, "categories"=>["Neuroscience", "Cell Biology", "Genetics"], "users"=>["Bo Xiong", "Vafa Bayat", "Manish Jaiswal", "Ke Zhang", "Hector Sandoval", "Wu-Lin Charng", "Tongchao Li", "Gabriela David", "Lita Duraine", "Yong-Qi Lin", "G. Gregory Neely", "Shinya Yamamoto", "Hugo J. Bellen"], "doi"=>"https://dx.doi.org/10.1371/journal.pbio.1001438.g004", "stats"=>{"downloads"=>1, "page_views"=>14, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Crag_is_required_for_Rh1_transport_to_the_rhabdomeres_upon_light_stimulation_/202170", "title"=>"Crag is required for Rh1 transport to the rhabdomeres upon light stimulation.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-12-04 00:36:10"}
  • {"files"=>["https://ndownloader.figshare.com/files/531838"], "description"=>"<p>(A) ERG traces of flies with expression of <i>UAS-GFP, Rab11-DN(S25N), Rab11</i> double-stranded RNA constructs <i>(Rab11 RNAi<sup>1</sup></i> and <i>Rab11 RNAi<sup>2</sup>), Rab11, Rab11-CA(Q70L)</i>, and <i>Rab10-DN(T23N)</i> driven by <i>Rh1-GAL4</i> at day 1 and day 21 with or without 12-h on/off light exposure (L/D). Note that the ERG amplitudes are reduced in the flies with Rab11 knockdown and light exposure (red box). (B) Quantification of ERG depolarization amplitudes shown in (A). Five ERG traces were measured for each genotype at each time point. An asterisk indicates a <i>p</i>-value less than 0.05; “n.s.” indicates a <i>p</i>-value greater than 0.05. (C) TEM of photoreceptor cross-sections of flies expressing GFP, Rab11-DN, or Rab11 RNAi<sup>2</sup> in photoreceptor cells after 21 d of incubation in light/dark cycle or in constant dark. Note that the rhabdomere morphology is disrupted in flies with Rab11 knockdown upon light exposure. Since Rh1-GAL4 drives expression only in R1–R6 photoreceptors, R7/R8 are better preserved than R1–R6. Scale bar, 1 µM.</p>", "links"=>[], "tags"=>["rab11", "causes", "light-dependent", "photoreceptor"], "article_id"=>202321, "categories"=>["Neuroscience", "Cell Biology", "Genetics"], "users"=>["Bo Xiong", "Vafa Bayat", "Manish Jaiswal", "Ke Zhang", "Hector Sandoval", "Wu-Lin Charng", "Tongchao Li", "Gabriela David", "Lita Duraine", "Yong-Qi Lin", "G. Gregory Neely", "Shinya Yamamoto", "Hugo J. Bellen"], "doi"=>"https://dx.doi.org/10.1371/journal.pbio.1001438.g005", "stats"=>{"downloads"=>1, "page_views"=>19, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Knockdown_of_Rab11_in_adult_eye_causes_light_dependent_photoreceptor_degeneration_/202321", "title"=>"Knockdown of Rab11 in adult eye causes light-dependent photoreceptor degeneration.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-12-04 00:38:41"}
  • {"files"=>["https://ndownloader.figshare.com/files/531222"], "description"=>"<p>(A) Representative ERG traces of 3-wk-old wild-type control flies (Ctrl; <i>y w FRT19A<sup>iso</sup></i>) and flies with <i>XE10</i> mutant clones. “On” and “off” transients are marked by red circles. (B) Quantification and statistics of ERG amplitude. Five ERG traces were measured for each genotype. An asterisk indicates a <i>p</i>-value less than 0.05. (C) <i>XE10</i> alleles fail to complement a lethal insertion, which is inserted in the first exon of <i>Crag</i>. The red dotted lines mark the region of overlap of the deficiencies that fail to complement the <i>XE10</i> mutations. (D) Structure of the <i>Crag</i> gene. A 12-kb genomic rescue construct <a href=\"http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1001438#pbio.1001438-Denef1\" target=\"_blank\">[8]</a> that covers 2 kb upstream and 1.5 kb downstream of the <i>Crag</i> coding region rescues the <i>XE10</i> alleles. (E) Lethal phase analysis of <i>Crag</i> alleles. In the upper four lines, lethal phases of transheterozygous animals were tested. For genomic rescue experiment, heterozygous female flies were crossed with males bearing the genomic rescue construct. Rescued male progenies were identified by males that do not carry the <i>FM7c</i> balancer. For human DENND4A rescue, <i>Crag<sup>(A, C, or D)</sup></i>, <i>FRT19A</i>/<i>FM7c</i>; <i>da-GAL4</i> flies were crossed with <i>UAS-DENND4A</i>, and the rescued male progenies were identified by loss of the balancer. (F) Molecular lesions identified in the three <i>Crag</i> alleles. (G) Eye imaginal discs containing <i>Crag<sup>C</sup></i> clones stained with a Crag antibody. GFP expression (green) marks wild-type (WT) cells, and Crag (red) punctae are detected in the cytosol of wild-type cells but not in <i>Crag<sup>C</sup></i> mutant cells.</p>", "links"=>[], "tags"=>["mutant", "photoreceptors", "abnormal", "corresponds"], "article_id"=>201698, "categories"=>["Neuroscience", "Cell Biology", "Genetics"], "users"=>["Bo Xiong", "Vafa Bayat", "Manish Jaiswal", "Ke Zhang", "Hector Sandoval", "Wu-Lin Charng", "Tongchao Li", "Gabriela David", "Lita Duraine", "Yong-Qi Lin", "G. Gregory Neely", "Shinya Yamamoto", "Hugo J. Bellen"], "doi"=>"https://dx.doi.org/10.1371/journal.pbio.1001438.g001", "stats"=>{"downloads"=>0, "page_views"=>14, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_XE10_mutant_photoreceptors_exhibit_abnormal_ERG_and_XE10_corresponds_to_Crag_/201698", "title"=>"<i>XE10</i> mutant photoreceptors exhibit abnormal ERG, and <i>XE10</i> corresponds to <i>Crag</i>.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-12-04 00:28:18"}
  • {"files"=>["https://ndownloader.figshare.com/files/532123"], "description"=>"<p>(A) Immunostaining of Crag (green) and Rab11 (red) in cross-sections of wild-type photoreceptors upon 12 h of light stimulation. The proteins colocalize in punctuate structures (indicated by arrowheads). The rhabdomeres are marked by Actin staining (blue). Scale bar, 5 µM. (B) Immunostaining of Rab11 (red) and Rh1 (green) in photoreceptors of wild-type controls and <i>Crag</i> mutants upon 12 h of light stimulation. In controls, Rab11 is present in punctae that partially colocalize with Rh1 (indicated by arrowheads), and most of the punctae are close to the rhabdomeres; in <i>Crag</i> mutants, many fewer punctae of Rab11 are observed, and these punctae are not closely associated with rhabdomeres (indicated by arrows). Scale bar, 5 µM. (C) GFP or Rab11-CA were expressed in <i>Crag</i> mutant clones, and the flies were kept in a 12 hour light/dark cycle (L/D) for 3 wk along with controls (<i>y w P{neoFRT}19A<sup>iso</sup></i> with GFP expression in the photoreceptors). Representative ERG traces of these flies are shown. (D) Quantification of the ERG depolarization amplitudes shown in (B). Ten ERG traces were measured for each genotype at each time point. An asterisk indicates a <i>p</i>-value less than 0.05. (E) Quantification of the ERG off-transient amplitudes shown in (B). Ten ERG traces were measured for each genotype at each time point. (F) TEM of photoreceptor cross-sections of flies expressing GFP or Rab11-CA in <i>Crag</i> mutant photoreceptor cells after 21 d of incubation in a light/dark cycle. The morphology of the rhabdomeres is much better preserved when Rab11-CA is expressed. Scale bar, 1 µM. (G) Model of Crag function. Upon absorption of a photon, Rh1 undergoes a conformational change to the active form, metaRh, which signals through a G-protein-coupled cascade and triggers the opening of TRP channels and the influx of Ca<sup>2+</sup> and Na<sup>+</sup> into photoreceptor cells. MetaRh is converted back into Rh1 by exposure to another photon. However, a subpopulation of Rh1 is endocytosed and degraded through a lysosomal pathway. To replenish the Rh1 pool, Rh1 needs to be synthesized and delivered to the rhabdomeres. Rab11-mediated vesicle trafficking is required for Rh1 transport to the rhabdomeres. Crag is a GEF for Rab11 in this process, and its GEF activity maybe enhanced by CaM and Ca<sup>2+</sup> influx. Hence, light stimulation not only triggers endocytosis but may also promote trafficking of Rh1 to rhabdomeres to maintain homeostasis. PLC, Phospholipase C.</p>", "links"=>[], "tags"=>["genetically", "interacts", "rab11"], "article_id"=>202607, "categories"=>["Neuroscience", "Cell Biology", "Genetics"], "users"=>["Bo Xiong", "Vafa Bayat", "Manish Jaiswal", "Ke Zhang", "Hector Sandoval", "Wu-Lin Charng", "Tongchao Li", "Gabriela David", "Lita Duraine", "Yong-Qi Lin", "G. Gregory Neely", "Shinya Yamamoto", "Hugo J. Bellen"], "doi"=>"https://dx.doi.org/10.1371/journal.pbio.1001438.g007", "stats"=>{"downloads"=>1, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Crag_genetically_interacts_with_Rab11_in_vivo_/202607", "title"=>"Crag genetically interacts with Rab11 in vivo.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-12-04 00:43:27"}
  • {"files"=>["https://ndownloader.figshare.com/files/531356"], "description"=>"<p>(A) ERG traces of wild-type control (<i>y w FRT19A<sup>iso</sup></i>) and <i>Crag</i> mutant clones in flies raised in a 12-h on/off light cycle (L/D), or in constant light, or in the dark at different ages. Note that both the depolarization amplitude and the size of “on” and “off” transients become smaller upon light/dark exposure in <i>Crag</i> mutants but are not affected in wild-type controls. Constant light triggers a more severe reduction of ERG amplitude in <i>Crag</i> mutant cells. These defects are strictly light-dependent and can be rescued by the genomic rescue construct. (B) TEM of ommatidia cross-sections. Rhabdomere structures are recognized by their high electron density. Note that the aged <i>Crag</i> mutant photoreceptor cells are largely disrupted (lower right). Scale bar, 1 µM. (C) Quantification of ERG depolarization amplitudes shown in (A). Ten ERG traces were measured for each genotype at each time point. An asterisk indicates a <i>p</i>-value less than 0.05; “n.s.” indicates a <i>p</i>-value greater than 0.05. (D) Quantification of ERG off-transient amplitudes shown in (A). Ten ERG traces were measured for each genotype at each time point. (E) Quantification of rhabdomere areas shown in (C). Rhabdomere area in <i>Crag</i> mutant photoreceptors is largely reduced after 2 wk of light exposure. The rhabdomeres were outlined and their sizes were calculated using Image J software. Ten ommatidia from different cross-sections were analyzed for each genotype.</p>", "links"=>[], "tags"=>["light-dependent", "photoreceptor"], "article_id"=>201840, "categories"=>["Neuroscience", "Cell Biology", "Genetics"], "users"=>["Bo Xiong", "Vafa Bayat", "Manish Jaiswal", "Ke Zhang", "Hector Sandoval", "Wu-Lin Charng", "Tongchao Li", "Gabriela David", "Lita Duraine", "Yong-Qi Lin", "G. Gregory Neely", "Shinya Yamamoto", "Hugo J. Bellen"], "doi"=>"https://dx.doi.org/10.1371/journal.pbio.1001438.g002", "stats"=>{"downloads"=>0, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Mutations_in_Crag_lead_to_a_light_dependent_photoreceptor_degeneration_/201840", "title"=>"Mutations in <i>Crag</i> lead to a light-dependent photoreceptor degeneration.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-12-04 00:30:40"}
  • {"files"=>["https://ndownloader.figshare.com/files/531514"], "description"=>"<p>(A) Whole mount staining of photoreceptors of flies raised in the dark. Note that Rh1, InaD, and TRP all exhibit crescent shaped patterns at the base of the rhabdomeres in both genotypes. Rhabdomeres are labeled by phalloidin staining of Actin. Scale bar, 5 µM. (B) Same staining as (A) in control (Ctrl) and <i>Crag</i> mutant flies upon 5 d of light/dark (L/D) exposure. Note the cytosolic accumulation of Rh1 in <i>Crag</i> mutant photoreceptors. (C) Cross-sections of control (<i>y w FRT19A<sup>iso</sup></i>) and <i>Crag</i> mutant photoreceptors in flies raised in dark were stained with antibody against Rh1, InaD, and TRP. All markers examined exhibit a normal distribution in both genotypes. Note that all the proteins are uniformly distributed in the rhabdomeres. Scale bar, 2 µM. (D) Same staining as (C) for flies exposed to 36 h of light and then kept for 12 h in the dark. Note that Rh1, but not InaD and TRP, is accumulated in the cytosol in <i>Crag</i> mutants. (E and F) TEM of a photoreceptor cross-section of a control and a <i>Crag</i> mutant photoreceptor upon 5 d of light/dark exposure. Note the accumulation of numerous vesicles (red arrows) in <i>Crag</i> mutant cells. Scale bar, 1 µM.</p>", "links"=>[], "tags"=>["accumulates", "cytosol", "mutant", "photoreceptor", "cells"], "article_id"=>201995, "categories"=>["Neuroscience", "Cell Biology", "Genetics"], "users"=>["Bo Xiong", "Vafa Bayat", "Manish Jaiswal", "Ke Zhang", "Hector Sandoval", "Wu-Lin Charng", "Tongchao Li", "Gabriela David", "Lita Duraine", "Yong-Qi Lin", "G. Gregory Neely", "Shinya Yamamoto", "Hugo J. Bellen"], "doi"=>"https://dx.doi.org/10.1371/journal.pbio.1001438.g003", "stats"=>{"downloads"=>0, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Rh1_accumulates_in_the_cytosol_of_Crag_mutant_photoreceptor_cells_upon_light_stimulation_/201995", "title"=>"Rh1 accumulates in the cytosol of <i>Crag</i> mutant photoreceptor cells upon light stimulation.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-12-04 00:33:15"}
  • {"files"=>["https://ndownloader.figshare.com/files/286327", "https://ndownloader.figshare.com/files/286340", "https://ndownloader.figshare.com/files/286362", "https://ndownloader.figshare.com/files/286401", "https://ndownloader.figshare.com/files/286413", "https://ndownloader.figshare.com/files/286433", "https://ndownloader.figshare.com/files/286452", "https://ndownloader.figshare.com/files/286469", "https://ndownloader.figshare.com/files/286488", "https://ndownloader.figshare.com/files/286552"], "description"=>"<div><p>Rhodopsins (Rhs) are light sensors, and Rh1 is the major Rh in the <em>Drosophila</em> photoreceptor rhabdomere membrane. Upon photoactivation, a fraction of Rh1 is internalized and degraded, but it remains unclear how the rhabdomeric Rh1 pool is replenished and what molecular players are involved. Here, we show that Crag, a DENN protein, is a guanine nucleotide exchange factor for Rab11 that is required for the homeostasis of Rh1 upon light exposure. The absence of Crag causes a light-induced accumulation of cytoplasmic Rh1, and loss of <em>Crag</em> or <em>Rab11</em> leads to a similar photoreceptor degeneration in adult flies. Furthermore, the defects associated with loss of <em>Crag</em> can be partially rescued with a constitutive active form of Rab11. We propose that upon light stimulation, Crag is required for trafficking of Rh from the trans-Golgi network to rhabdomere membranes via a Rab11-dependent vesicular transport.</p> </div>", "links"=>[], "tags"=>["crag", "gef", "rab11", "rhodopsin", "trafficking", "photoreceptor", "cells"], "article_id"=>116435, "categories"=>["Neuroscience", "Cell Biology", "Genetics"], "users"=>["Bo Xiong", "Vafa Bayat", "Manish Jaiswal", "Ke Zhang", "Hector Sandoval", "Wu-Lin Charng", "Tongchao Li", "Gabriela David", "Lita Duraine", "Yong-Qi Lin", "G. Gregory Neely", "Shinya Yamamoto", "Hugo J. Bellen"], "doi"=>["https://dx.doi.org/10.1371/journal.pbio.1001438.s001", "https://dx.doi.org/10.1371/journal.pbio.1001438.s002", "https://dx.doi.org/10.1371/journal.pbio.1001438.s003", "https://dx.doi.org/10.1371/journal.pbio.1001438.s004", "https://dx.doi.org/10.1371/journal.pbio.1001438.s005", "https://dx.doi.org/10.1371/journal.pbio.1001438.s006", "https://dx.doi.org/10.1371/journal.pbio.1001438.s007", "https://dx.doi.org/10.1371/journal.pbio.1001438.s008", "https://dx.doi.org/10.1371/journal.pbio.1001438.s009", "https://dx.doi.org/10.1371/journal.pbio.1001438.s010"], "stats"=>{"downloads"=>1, "page_views"=>73, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Crag_Is_a_GEF_for_Rab11_Required_for_Rhodopsin_Trafficking_and_Maintenance_of_Adult_Photoreceptor_Cells__/116435", "title"=>"Crag Is a GEF for Rab11 Required for Rhodopsin Trafficking and Maintenance of Adult Photoreceptor Cells", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2012-12-04 01:47:15"}
  • {"files"=>["https://ndownloader.figshare.com/files/531982"], "description"=>"<p>(A) Immunostaining of S2 cells transfected with FLAG-tagged Crag (green) and HA-tagged Rab11 (red). Their expression regions largely overlap. Scale bar, 2 µM. (B) Immunostaining of S2 cells transfected with FLAG-tagged Crag and HA-tagged Rab7. No significant colocalization is observed. (C) S2 cells transfected with FLAG-tagged Crag and/or HA-tagged Rab11, Rab11-DN, or Rab11-CA were harvested and lysed. Anti-HA gel was used to pull down HA-tagged proteins. When Rab11 and Crag are co-transfected, Crag was also co-immunoprecipitated, as detected on Western blots, indicating that Crag binds to Rab11. Also note that Crag preferentially binds to the DN form of Rab11 rather than the CA form. (D) Quantification and statistics of binding affinity between Crag and the different forms of Rab11 shown in (A). The data are quantified using the Gel analysis function in Image J. Results from three independent experiments were analyzed. An asterisk indicates a <i>p</i>-value less than 0.05. (E) A scheme of different Crag deletion constructs and their binding affinity with Rab11 was tested by co-IPs. Crag segments containing DENN domains (DENN and DC) bind to Rab11, whereas the segments that lack DENN domains (NT, CBS, and CT) do not, indicating that the interaction between Crag and Rab11 is dependent on DENN domains. (F) GEF assay of Crag and Rab10. Crag and Rab10 proteins were purified using a baculovirus system. Rab10 was preloaded with fluorescence-labeled BODIPY-GDP, and then GTP was added with or without Crag. The change of fluorescence intensity was recorded for 2 h. Crag promotes the release of GDP from Rab10, indicating it possesses GEF activity against Rab10. (G) GEF assay of Crag and Rab11. Crag promotes GDP release from Rab11, and the presence of CaM and calcium further enhances the release rate. 10 mM EDTA was used as a positive control, as EDTA absorbs Mg<sup>2+</sup> from Rab11 and triggers GDP release. (H) GEF assay of Crag and Rab5. No GEF activity against Rab5 was observed, whereas 10 mM EDTA triggers a rapid release of GDP from Rab5.</p>", "links"=>[], "tags"=>["interacts", "rab11"], "article_id"=>202465, "categories"=>["Neuroscience", "Cell Biology", "Genetics"], "users"=>["Bo Xiong", "Vafa Bayat", "Manish Jaiswal", "Ke Zhang", "Hector Sandoval", "Wu-Lin Charng", "Tongchao Li", "Gabriela David", "Lita Duraine", "Yong-Qi Lin", "G. Gregory Neely", "Shinya Yamamoto", "Hugo J. Bellen"], "doi"=>"https://dx.doi.org/10.1371/journal.pbio.1001438.g006", "stats"=>{"downloads"=>0, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Crag_interacts_with_Rab11_in_vitro_/202465", "title"=>"Crag interacts with Rab11 in vitro.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-12-04 00:41:05"}

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Relative Metric

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