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

Pei-Wen Chiang, Naoki Oiso, Rashi Gautam, Tamio Suzuki, Richard T. Swank, Richard A. Spritz

Research output: Contribution to journalArticle

75 Citations (Scopus)

Abstract

Hermansky-Pudlak syndrome (HPS) is a genetic disease of lysosome, melanosome, and granule biogenesis. Mutations of six different loci have been associated with HPS in humans, the most frequent of which are mutations of the HPS1 and HPS4 genes. Here, we show that the HPS1 and HPS4 proteins are components of two novel protein complexes involved in biogenesis of melanosome and lysosome-related organelles: biogenesis of lysosome-related organelles complex-(BLOC) 3 and BLOC-4. The phenotypes of Hps1-mutant (pale-ear; ep) and Hps4-mutant (light-ear; le) mice and humans are very similar, and cells from ep and le mice exhibit similar abnormalities of melanosome morphology. HPS1 protein is absent from ep-mutant cells, and HPS4 from le-mutant cells, but le-mutant cells also lack HPS1 protein. HPS4 protein seems to be necessary for stabilization of HPS1, and the HPS1 and HPS4 proteins co-immunoprecipitate, indicating that they are in a complex. HPS1 and HPS4 do not interact directly in a yeast two-hybrid system, although HPS4 interacts with itself. In a partially purified vesicular/organellar fraction, HPS1 and HPS4 are both components of a complex with a molecular mass of ∼500 kDa, termed BLOC-3. Within BLOC-3, HPS1 and HPS4 are components of a discrete ∼200-kDa module termed BLOC-4. In the cytosol, HPS1 (but not HPS4) is part of yet another complex, termed BLOC-5. We propose that the BLOC-3 and BLOC-4 HPS1·HPS4 complexes play a central role in trafficking cargo proteins to newly formed cytoplasmic organelles.

Original languageEnglish (US)
Pages (from-to)20332-20337
Number of pages6
JournalJournal of Biological Chemistry
Volume278
Issue number22
DOIs
StatePublished - May 30 2003
Externally publishedYes

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Hermanski-Pudlak Syndrome
Lysosomes
Organelles
Proteins
Melanosomes
Molecular mass
Ear
Hybrid systems
Yeast
Stabilization
Genes
Two-Hybrid System Techniques
Mutation
Inborn Genetic Diseases
Organelle Biogenesis
Protein Transport

ASJC Scopus subject areas

  • Biochemistry

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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. / Chiang, Pei-Wen; Oiso, Naoki; Gautam, Rashi; Suzuki, Tamio; Swank, Richard T.; Spritz, Richard A.

In: Journal of Biological Chemistry, Vol. 278, No. 22, 30.05.2003, p. 20332-20337.

Research output: Contribution to journalArticle

Chiang, Pei-Wen ; Oiso, Naoki ; Gautam, Rashi ; Suzuki, Tamio ; Swank, Richard T. ; Spritz, Richard A. / 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. In: Journal of Biological Chemistry. 2003 ; Vol. 278, No. 22. pp. 20332-20337.
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abstract = "Hermansky-Pudlak syndrome (HPS) is a genetic disease of lysosome, melanosome, and granule biogenesis. Mutations of six different loci have been associated with HPS in humans, the most frequent of which are mutations of the HPS1 and HPS4 genes. Here, we show that the HPS1 and HPS4 proteins are components of two novel protein complexes involved in biogenesis of melanosome and lysosome-related organelles: biogenesis of lysosome-related organelles complex-(BLOC) 3 and BLOC-4. The phenotypes of Hps1-mutant (pale-ear; ep) and Hps4-mutant (light-ear; le) mice and humans are very similar, and cells from ep and le mice exhibit similar abnormalities of melanosome morphology. HPS1 protein is absent from ep-mutant cells, and HPS4 from le-mutant cells, but le-mutant cells also lack HPS1 protein. HPS4 protein seems to be necessary for stabilization of HPS1, and the HPS1 and HPS4 proteins co-immunoprecipitate, indicating that they are in a complex. HPS1 and HPS4 do not interact directly in a yeast two-hybrid system, although HPS4 interacts with itself. In a partially purified vesicular/organellar fraction, HPS1 and HPS4 are both components of a complex with a molecular mass of ∼500 kDa, termed BLOC-3. Within BLOC-3, HPS1 and HPS4 are components of a discrete ∼200-kDa module termed BLOC-4. In the cytosol, HPS1 (but not HPS4) is part of yet another complex, termed BLOC-5. We propose that the BLOC-3 and BLOC-4 HPS1·HPS4 complexes play a central role in trafficking cargo proteins to newly formed cytoplasmic organelles.",
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T1 - 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

AU - Chiang, Pei-Wen

AU - Oiso, Naoki

AU - Gautam, Rashi

AU - Suzuki, Tamio

AU - Swank, Richard T.

AU - Spritz, Richard A.

PY - 2003/5/30

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AB - Hermansky-Pudlak syndrome (HPS) is a genetic disease of lysosome, melanosome, and granule biogenesis. Mutations of six different loci have been associated with HPS in humans, the most frequent of which are mutations of the HPS1 and HPS4 genes. Here, we show that the HPS1 and HPS4 proteins are components of two novel protein complexes involved in biogenesis of melanosome and lysosome-related organelles: biogenesis of lysosome-related organelles complex-(BLOC) 3 and BLOC-4. The phenotypes of Hps1-mutant (pale-ear; ep) and Hps4-mutant (light-ear; le) mice and humans are very similar, and cells from ep and le mice exhibit similar abnormalities of melanosome morphology. HPS1 protein is absent from ep-mutant cells, and HPS4 from le-mutant cells, but le-mutant cells also lack HPS1 protein. HPS4 protein seems to be necessary for stabilization of HPS1, and the HPS1 and HPS4 proteins co-immunoprecipitate, indicating that they are in a complex. HPS1 and HPS4 do not interact directly in a yeast two-hybrid system, although HPS4 interacts with itself. In a partially purified vesicular/organellar fraction, HPS1 and HPS4 are both components of a complex with a molecular mass of ∼500 kDa, termed BLOC-3. Within BLOC-3, HPS1 and HPS4 are components of a discrete ∼200-kDa module termed BLOC-4. In the cytosol, HPS1 (but not HPS4) is part of yet another complex, termed BLOC-5. We propose that the BLOC-3 and BLOC-4 HPS1·HPS4 complexes play a central role in trafficking cargo proteins to newly formed cytoplasmic organelles.

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