BLOC-3, a Protein Complex Containing the Hermansky-Pudlak Syndrome Gene Products HPS1 and HPS4*

The Hermansky-Pudlak syndrome (HPS) is a genetic disorder characterized by defective lysosome-related organelles. HPS results from mutations in either one of six human genes named HPS1 to HPS6, most of which encode proteins of unknown function. Here we report that the human HPS1 and HPS4 proteins are part of a complex named BLOC-3 (for biogenesis of lysosome-related organelles complex 3). Co-immunoprecipitation experiments demonstrated that epitope-tagged and endogenous HPS1 and HPS4 proteins assemble with each other in vivo. The HPS1·HPS4 complex is predominantly cytosolic, with a small amount being peripherally associated with membranes. Size exclusion chromatography and sedimentation velocity analyses of the cytosolic fraction indicate that HPS1 and HPS4 form a moderately asymmetric protein complex with a molecular mass of ∼175 kDa. HPS4-deficient fibroblasts from light ear mice display normal distribution and trafficking of the lysosomal membrane protein, Lamp-2, in contrast to fibroblasts from AP-3-deficient pearl mice (HPS2), which exhibit increased trafficking of this lysosomal protein via the plasma membrane. Similarly, light ear fibroblasts display an apparently normal accumulation of Zn2+ in intracellular vesicles, unlike pearl fibroblasts, which exhibit a decreased intracellular Zn2+ storage. Taken together, these 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.

• Publication year

  2003

• Venue

  Journal of Biological Chemistry

• Publication date

  2003-08-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1074/JBC.M301294200PMID 12756248
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• HPS4-deficient fibroblasts retain normal Lamp-2 trafficking and intracellular Zn2+ storage, unlike AP-3 complex-deficient pearl fibroblasts.

  Confidence 0.94

  박진우 (dztg5apj7m) extraction뀨 (7c402c1b98) reviewB (s683577b42) reviewAK (4715169a40) review
• The HPS1/HPS4 complex is predominantly cytosolic, with a smaller fraction associated peripherally with membranes, and has an estimated molecular mass of about 175 kDa.

  Confidence 0.95

  박진우 (dztg5apj7m) extraction뀨 (7c402c1b98) reviewB (s683577b42) reviewAK (4715169a40) review
• HPS1 and HPS4 assemble in vivo into the BLOC-3 protein complex.

  Confidence 0.98

  박진우 (dztg5apj7m) extraction뀨 (7c402c1b98) reviewB (s683577b42) reviewAK (4715169a40) review

• ap-3 complex

  protein complex

  An adaptor protein complex used here as a trafficking-related comparison for lysosomal protein sorting.

  박진우 (dztg5apj7m) extraction뀨 (7c402c1b98) reviewB (s683577b42) reviewAK (4715169a40) review
• bloc-3

  protein complex

  The biogenesis of lysosome-related organelles complex 3 named for the HPS1/HPS4 assembly.

  Aliases: biogenesis of lysosome-related organelles complex 3

  박진우 (dztg5apj7m) extraction뀨 (7c402c1b98) reviewB (s683577b42) reviewAK (4715169a40) review
• hps1

  protein, gene product

  A human Hermansky-Pudlak syndrome gene product examined as part of the BLOC-3 complex.

  박진우 (dztg5apj7m) extraction뀨 (7c402c1b98) reviewB (s683577b42) reviewAK (4715169a40) review
• hps1/hps4 complex

  protein complex

  The cytosolic protein assembly composed of HPS1 and HPS4.

  Aliases: HPS1·HPS4 complex

  박진우 (dztg5apj7m) extraction뀨 (7c402c1b98) reviewB (s683577b42) reviewAK (4715169a40) review
• hps4

  protein, gene product

  A human Hermansky-Pudlak syndrome gene product examined as part of the BLOC-3 complex.

  박진우 (dztg5apj7m) extraction뀨 (7c402c1b98) reviewB (s683577b42) reviewAK (4715169a40) review
• intracellular zn2+ storage

  cellular phenotype, ion storage

  The accumulation of zinc inside intracellular vesicles used as a readout of lysosome-related organelle function.

  Aliases: intracellular zinc storage

  박진우 (dztg5apj7m) extraction뀨 (7c402c1b98) reviewB (s683577b42) reviewAK (4715169a40) review
• lamp-2

  protein, membrane protein

  A lysosomal membrane protein used as a marker for intracellular trafficking in fibroblasts.

  박진우 (dztg5apj7m) extraction뀨 (7c402c1b98) reviewB (s683577b42) reviewAK (4715169a40) review
• lysosome-related organelles

  organelle, cellular structure

  Specialized organelles with lysosome-like functions that are affected in Hermansky-Pudlak syndrome.

  Aliases: LROs

  박진우 (dztg5apj7m) extraction뀨 (7c402c1b98) reviewB (s683577b42) reviewAK (4715169a40) review

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