Characterization of BLOC‐2, a Complex Containing the Hermansky–Pudlak Syndrome Proteins HPS3, HPS5 and HPS6

@article{DiPietro2004CharacterizationOB,
  title={Characterization of BLOC‐2, a Complex Containing the Hermansky–Pudlak Syndrome Proteins HPS3, HPS5 and HPS6},
  author={Santiago M. Di Pietro and Juan Manuel Falc{\'o}n-P{\'e}rez and Esteban C Dell'Angelica},
  journal={Traffic},
  year={2004},
  volume={5}
}
Hermansky–Pudlak syndrome (HPS) defines a group of at least seven autosomal recessive disorders characterized by albinism and prolonged bleeding due to defects in the lysosome‐related organelles, melanosomes and platelet‐dense granules, respectively. Most HPS genes, including HPS3, HPS5 and HPS6, encode ubiquitously expressed novel proteins of unknown function. Here, we report the biochemical characterization of a stable protein complex named Biogenesis of Lysosome‐related Organelles Complex‐2… 
Association of the Hermansky-Pudlak syndrome type-3 protein with clathrin
TLDR
A role for HPS3 and its protein complex, BLOC-2, in vesicle formation and trafficking is suggested, predominantly on small clathrin-containing vesicles in the perinuclear region.
Identification of Snapin and Three Novel Proteins (BLOS1, BLOS2, and BLOS3/Reduced Pigmentation) as Subunits of Biogenesis of Lysosome-related Organelles Complex-1 (BLOC-1)*
TLDR
Mutations in the human genes encoding Snapin and the BLOS proteins could underlie novel forms of HPS, and Yeast two-hybrid analyses suggest a network of binary interactions involving all of the previously known and newly identified subunits.
A Novel Likely Pathogenic Variant in the BLOC1S5 Gene Associated with Hermansky-Pudlak Syndrome Type 11 and an Overview of Human BLOC-1 Deficiencies
TLDR
The aim was to unravel the genetic defect in two siblings with a suspected HPS diagnosis (because of OCA and bleeding symptoms) using next generation sequencing (NGS), which revealed reduced platelet aggregation after stimulation with ADP and a severe secretion defect in platelet δ-granules.
Clinical and cellular characterisation of Hermansky–Pudlak syndrome type 6
TLDR
The HPS-6 subtype resembles other BLOC-2 defective subtypes in its molecular, cellular and clinical findings, and is important for providing a prognosis to newly diagnosed H PS patients, but also for further elucidation of HPS function in the biogenesis of LROs.
Identifying Putative Promoter Regions of Hermansky‐Pudlak Syndrome Genes by Means of Phylogenetic Footprinting
TLDR
These findings illustrate the power of phylogenetic footprinting for identifying potential regulatory regions in non‐coding sequences and define the first putative promoter elements for any HPS genes.
Molecular Genetics of Hermansky–Pudlak Syndrome
TLDR
Novel players of LRO biogenesis are revealed by human disease and animal mutations, which continue to provide invaluable resources for elucidating the complex pathways involved in the biogenesis of these organelles.
Cellular and molecular defects in a patient with Hermansky-Pudlak syndrome type 5
TLDR
The results suggest the role of HPS5 in the endo-lysosomal dynamics of skin fibroblasts and present an HPS patient with defective BLOC-2 due to a novel intronic mutation in H PS5 that activates a cryptic acceptor splice site.
Hermansky-Pudlak Syndrome: Identification of Novel Variants in the Genes HPS3, HPS5, and DTNBP1 (HPS-7)
TLDR
This work investigated three patients (IP1, IP2, and IP3) who suffer from a bleeding diathesis and identified a homozygous deletion of exon 6 in DTNBP1 for IP3, which confirmed the absence of the encoded protein dysbindin confirming the diagnosis of HPS-7.
Improper trafficking of melanocyte-specific proteins in Hermansky-Pudlak syndrome type-5.
TLDR
Early stage melanosome formation and Pmel17 trafficking are preserved in HPS5-deficient cells, and Tyrosinase and TYRP1 are mistrafficked, however, and fail to be efficiently delivered to melanosomes of HPS-5 melanocytes.
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BLOC-3, a Protein Complex Containing the Hermansky-Pudlak Syndrome Gene Products HPS1 and HPS4*
TLDR
Observations demonstrate that the HPS1 and HPS4 proteins are components of a cytosolic complex that is involved in the biogenesis of lysosomal-related organelles by a mechanism distinct from that operated by AP-3 complex.
Biogenesis of lysosome-related organelles complex 3 (BLOC-3): A complex containing the Hermansky–Pudlak syndrome (HPS) proteins HPS1 and HPS4
TLDR
Observations suggest that HPS1 and HPS4 are components of a protein complex that regulates the intracellular localization of lysosome and late endosomes and may function in a BLOC-1-dependent pathway for melanosome biogenesis.
The Hermansky-Pudlak Syndrome 3 (Cocoa) Protein Is a Component of the Biogenesis of Lysosome-related Organelles Complex-2 (BLOC-2)*
TLDR
Results indicate that the Hps3, Hps5, and Hps6 proteins regulate vesicle trafficking to lysosome-related organelles at the physiological level as components of the BLOC-2 protein complex and suggest that the pathogenesis and future therapies of HPS 3, HPS5 and HPS6 patients are likely to be similar.
The Hermansky-Pudlak Syndrome 1 (HPS1) and HPS4 Proteins Are Components of Two Complexes, BLOC-3 and BLOC-4, Involved in the Biogenesis of Lysosome-related Organelles*
TLDR
It is proposed that the BLOC-3 andBLOC-4 HPS1·HPS4 complexes play a central role in trafficking cargo proteins to newly formed cytoplasmic organelles.
Hermansky-Pudlak syndrome type 7 (HPS-7) results from mutant dysbindin, a member of the biogenesis of lysosome-related organelles complex 1 (BLOC-1)
TLDR
It is shown that BLOC-1 is important in producing the HPS phenotype in humans, it is indicated that dysbindin has a role in the biogenesis of lysosome-related organelles and unexpected interactions between components of DPC and BL OC-1 are identified.
Hermansky–Pudlak Syndrome and Related Disorders of Organelle Formation
TLDR
Each gene responsible for a subset of HPS or a related disorder codes for a protein which almost certainly plays a pivotal role in vesicular trafficking, inextricably linking clinical and cell biological interests in this group of diseases.
BLOC-1, a Novel Complex Containing the Pallidin and Muted Proteins Involved in the Biogenesis of Melanosomes and Platelet-dense Granules*
TLDR
It is proposed that BLOC-1 mediates the biogenesis of lysosome-related organelles by a mechanism that may involve self-assembly and interaction with the actin cytoskeleton.
Mouse models of Hermansky Pudlak syndrome: a review.
TLDR
The recent molecular identification of the gene causing a major form of human HPS and the expected identifications of several mouse HPS genes are expected to increase the authors' understanding of intracellular vesicle trafficking, lead to discovery of new human H PS genes, and suggest diagnostic and therapeutic approaches toward the more severe clinical consequences of the disease.
The mouse organellar biogenesis mutant buff results from a mutation in Vps33a, a homologue of yeast vps33 and Drosophila carnation
In the mouse, more than 16 loci are associated with mutant phenotypes that include defective pigmentation, aberrant targeting of lysosomal enzymes, prolonged bleeding, and immunodeficiency, the
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