Thepinkgene encodes theDrosophilaorthologue of the human Hermansky–Pudlak syndrome 5 (HPS5) gene

Syrzycka, Monika; McEachern, Lori A.; Kinneard, Jennifer KinneardJ.; Prabhu, Kristel PrabhuK.; Fitzpatrick, Kathleen FitzpatrickK.; Schulze, S; Rawls, John M.; Lloyd, Vett K.; Sinclair, Donald A. R.; Honda, Barry M.

doi:10.1139/g07-032

Cited by 22 publications

(16 citation statements)

References 45 publications

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“…hps5 I76N is the first nontruncation mutation characterized in the hps5 WD40 domain Mutations in HPS5 have been identified in human HPS patients Huizing et al 2004;Korswagen et al 2008;Carmona-Rivera et al 2011), and several mutant alleles exist in mouse (ruby-eye 2, Nguyen et al 2002;Zhang et al 2003;Hirobe et al 2011) and in Drosophila (pink, Falcón -Perez et al 2007;Syrzycka et al 2007). Importantly, almost all of the characterized mutations in mouse or Drosophila result in a frameshift and premature truncation of Hps5.…”

Section: Discussionmentioning

confidence: 99%

snow white, a Zebrafish Model of Hermansky-Pudlak Syndrome Type 5

et al. 2013

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Hermansky-Pudlak Syndrome (HPS) is a set of genetically heterogeneous diseases caused by mutations in one of nine known HPS genes. HPS patients display oculocutaneous hypopigmentation and bleeding diathesis and, depending on the disease subtype, pulmonary fibrosis, congenital nystagmus, reduced visual acuity, and platelet aggregation deficiency. Mouse models for all known HPS subtypes have contributed greatly to our understanding of the disease, but many of the molecular and cellular mechanisms underlying HPS remain unknown. Here, we characterize ocular defects in the zebrafish (Danio rerio) mutant snow white (snw), which possesses a recessive, missense mutation in hps5 (hps5 I76N ). Melanosome biogenesis is disrupted in snw/hps5 mutants, resulting in hypopigmentation, a significant decrease in the number, size, and maturity of melanosomes, and the presence of ectopic multimelanosome clusters throughout the mutant retina and choroid. snw/hps5 I76N is the first Hps5 mutation identified within the N-terminal WD40 repeat protein-protein binding domain. Through in vitro coexpression assays, we demonstrate that Hps5 I76N retains the ability to bind its protein complex partners, Hps3 and Hps6. Furthermore, while Hps5 and Hps6 stabilize each other's expression, this stabilization is disrupted by Hps5 I76N . The snw/hps5 I76N mutant provides a valuable resource for structure-function analyses of Hps5 and enables further elucidation of the molecular and cellular mechanisms underlying HPS.

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Section: Discussionmentioning

confidence: 99%

snow white, a Zebrafish Model of Hermansky-Pudlak Syndrome Type 5

et al. 2013

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“…The three murine ruby eye‐2 HPS5 mutations are p.G757delGinsTT ( ru2 1 ), p.E900insCCGG ( ru2 hz ) or p.K867ins\∼1 kb ( ru2 ), and are all associated with hypopigmentation and prolonged bleeding (6). In addition, the Drosophila melanogaster eye colour mutant pink was recently shown to be mutated (p.Q846delA) in the fly homologue of HPS5 (19). Both the murine and fly mutations occur further into the protein than our human mutation at codon 297.…”

Section: Discussionmentioning

confidence: 99%

A novel mutation in a Turkish patient with Hermansky–Pudlak syndrome type 5

Korswagen

Huizing

Şimşek

et al. 2007

European J of Haematology

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The Hermansky-Pudlak syndrome (HPS) is a rare genetically heterogeneous autosomal recessive disorder, characterized by tyrosinase-positive oculocutaneous albinism, platelet dysfunction and lysosomal ceroid lipofuscin storage. This is caused by defects in lysosome-related organelles. In humans eight different types of the syndrome are known, of which a short overview is given. The clinical features and a novel mutation of a patient with HPS type 5 are described here.

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“…Eight proteins composing the BLOC-1 and BLOC-2 complexes that function in LRO biogenesis in mammals (Raposo et al 2007), are found only in metazoans (Dell'angelica 2004). Nearly all of the subunits of the BLOC-1 and BLOC-2 complexes are conserved in Drosophila, where at least one subunit is glo-3 and Gut Granule Biogenesisnecessary for the biogenesis of a LRO (Falcon-Perez et al 2007;Syrzycka et al 2007). Notably, few BLOC-1 or BLOC-2 subunits are obviously conserved in C. elegans (De Voer et al 2008).…”

Section: ) Had Similar Localizations and Morphologies Inmentioning

confidence: 99%

glo-3, a Novel Caenorhabditis elegans Gene, Is Required for Lysosome-Related Organelle Biogenesis

Rabbitts¹,

Ciotti

Miller

et al. 2008

Genetics

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Gut granules are specialized lysosome-related organelles that act as sites of fat storage in Caenorhabditis elegans intestinal cells. We identified mutations in a gene, glo-3, that functions in the formation of embryonic gut granules. Some glo-3(À) alleles displayed a complete loss of embryonic gut granules, while other glo-3(À) alleles had reduced numbers of gut granules. A subset of glo-3 alleles led to mislocalization of gut granule contents into the intestinal lumen, consistent with a defect in intracellular trafficking. glo-3(À) embryos lacking gut granules developed into adults containing gut granules, indicating that glo-3(1) function may be differentially required during development. We find that glo-3(1) acts in parallel with or downstream of the AP-3 complex and the PGP-2 ABC transporter in gut granule biogenesis. glo-3 encodes a predicted membrane-associated protein that lacks obvious sequence homologs outside of nematodes. glo-3 expression initiates in embryonic intestinal precursors and persists almost exclusively in intestinal cells through adulthood. GLO-3TGFP localizes to the gut granule membrane, suggesting it could play a direct role in the trafficking events at the gut granule. smg-1(À) suppression of glo-3(À) nonsense alleles indicates that the C-terminal half of GLO-3, predicted to be present in the cytoplasm, is not necessary for gut granule formation. Our studies identify GLO-3 as a novel player in the formation of lysosome-related organelles.

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Thepinkgene encodes theDrosophilaorthologue of the human Hermansky–Pudlak syndrome 5 (HPS5) gene

Cited by 22 publications

References 45 publications

snow white, a Zebrafish Model of Hermansky-Pudlak Syndrome Type 5

snow white, a Zebrafish Model of Hermansky-Pudlak Syndrome Type 5

A novel mutation in a Turkish patient with Hermansky–Pudlak syndrome type 5

glo-3, a Novel Caenorhabditis elegans Gene, Is Required for Lysosome-Related Organelle Biogenesis

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