This report includes information relevant to a potential model of Hermansky-Pudlak syndrome 2 (HPS2), which is a subtype of Hermansky-Pudlak syndrome; HPS2 exhibits autosomal recessive inheritance. The human gene implicated in this disease is AP3B1, which encodes the beta 1 subunit of the non-clathrin- and clathrin-associated adaptor protein complex 3 (AP-3) that plays a role in protein sorting in the late-Golgi/trans-Golgi network (TGN) and/or endosomes. There is one high-scoring fly ortholog, rb, for which RNAi targeting constructs, alleles caused by insertional mutagenesis, and classical alleles have been generated.
AP3B1 has not yet been introduced into flies.
[updated Jul. 2017 by FlyBase; FBrf0222196]
Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive disorder in which oculocutaneous albinism, bleeding, and lysosomal ceroid storage result from defects of multiple cytoplasmic organelles: melanosomes, platelet-dense granules, and lysosomes (Oh et al., 1998, pubmed:9497254). [from MIM:115200, 2016.03.25]
Hermansky-Pudlak syndrome (HPS) is a multisystem disorder characterized by: tyrosinase-positive oculocutaneous albinism; a bleeding diathesis resulting from a platelet storage pool deficiency; and, in some cases, pulmonary fibrosis, granulomatous colitis, or immunodeficiency. The albinism is characterized by: hypopigmentation of the skin and hair; and ocular findings of reduced iris pigment with iris transillumination, reduced retinal pigment, foveal hypoplasia with significant reduction in visual acuity (usually in the range of 20/50 to 20/400), nystagmus, and increased crossing of the optic nerve fibers. Hair color ranges from white to brown; skin color ranges from white to olive and is usually a shade lighter than that of other family members. The bleeding diathesis can result in easy bruising, frequent epistaxis, gingival bleeding, postpartum hemorrhage, colonic bleeding, and prolonged bleeding with menses or after tooth extraction, circumcision, and other surgeries. Pulmonary fibrosis, a restrictive lung disease, typically causes symptoms in the early thirties and can progress to death within a decade. Granulomatous colitis is severe in about 15% of affected individuals. Neutropenia and/or immune defects are associated primarily with HPS-2. [from GeneReviews, Hermansky-Pudlak Syndrome, pubmed:20301486 2016.01.26]
[HERMANSKY-PUDLAK SYNDROME 2; HPS2](https://omim.org/entry/608233)
[ADAPTOR-RELATED PROTEIN COMPLEX 3, BETA-1 SUBUNIT; AP3B1](https://omim.org/entry/603401)
Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive disease characterized by platelet defects and oculocutaneous albinism. HPS2 differs from the other forms of HPS in that it includes immunodeficiency, and patients with HPS2 have an increased susceptibility to infections due to congenital neutropenia (Jung et al., 2006, pubmed:16537806). [From MIM:608233, 2016.03.24]
Hermansky-Pudlak syndrome-2 (HPS2) is caused by homozygous or compound heterozygous mutation in the gene encoding the beta-3A subunit of the AP3 complex (AP3B1). [From MIM:608233, 2016.03.24]
The fibroblasts of HPS2 patients exhibited drastically reduced levels of AP3 due to enhanced degradation of mutant beta-3A. The AP3 deficiency resulted in increased surface expression of the lysosomal membrane proteins CD63 (MIM:155740), LAMP1 (MIM:153330), and LAMP2 (MIM:309060), but not of nonlysosomal proteins. These differential effects are consistent with the preferential interaction of the AP3 mu-3A subunit with tyrosine-based signals involved in lysosomal targeting. These observations suggest that AP3 functions in protein sorting to lysosomes and that HPS provides an example of a human disease in which altered trafficking of integral membrane proteins is due to mutations in a component of the sorting machinery (Dell'Angelica et al.,1999, pubmed:10024875). CD8 (see MIM:186910)-positive cytotoxic T lymphocytes (CTLs) from an immunodeficient HPS2 patient lacked the beta-3A, gamma, and mu-3A subunits of AP3, consistent with HPS2. AP3 deficiency results in loss of microtubule-mediated movement of enlarged perforin- and granzyme-containing lytic granules toward the immunologic synapse and a profound loss of CTL-mediated killing(Clark et al., 2003, pubmed:14566336). [From MIM:608233 and MIM:603401, 2016.03.28]
The AP3B1 gene encodes the large B1 subunit of the adaptor-related protein complex-3, a heterotetrameric complex involved in protein trafficking to lysosomes or specialized endosomal-lysosomal organelles such as pigment granules, melanosomes, and platelet dense granules (Dell'Angelica et al., 1998, pubmed:9545220). Adaptor protein-3 (AP3) is a ubiquitous cytoplasmic complex that shuttles cargo proteins from the trans-Golgi and a tubular-endosomal compartment to endosome-lysosome-related organelles. Lack of the beta-3A subunit of this complex causes Hermansky-Pudlak syndrome type 2 (Fontana et al., 2006, pubmed:16507770). [From MIM:603401 and MIM:608233, 2016.03.28]
Many to one: 2 human to 1 Drosophila.
