Hermansky-Pudlak syndrome: a disease of protein trafficking and organelle function

Pigment Cell Res. 2006 Feb;19(1):19-42. doi: 10.1111/j.1600-0749.2005.00289.x.

Abstract

The Hermansky-Pudlak syndrome (HPS) is a collection of related autosomal recessive disorders which are genetically heterogeneous. There are eight human HPS subtypes, characterized by oculocutaneous albinism and platelet storage disease; prolonged bleeding, congenital neutropenia, pulmonary fibrosis, and granulomatous colitis can also occur. HPS is caused primarily by defects in intracellular protein trafficking that result in the dysfunction of intracellular organelles known as lysosome-related organelles. HPS gene products are all ubiquitously expressed and all associate in various multi-protein complexes, yet HPS has cell type-specific disease expression. Impairment of specialized secretory cells such as melanocytes, platelets, lung alveolar type II epithelial cells and cytotoxic T cells are observed in HPS. This review summarizes recent molecular, biochemical and cell biological analyses together with clinical studies that have led to the correlation of molecular pathology with clinical manifestations and led to insights into such diverse disease processes such as albinism, fibrosis, hemorrhage, and congenital neutropenia.

Publication types

  • Review

MeSH terms

  • Adaptor Protein Complex 3
  • Adaptor Protein Complex beta Subunits
  • Animals
  • Biological Transport*
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Disease Models, Animal
  • Dysbindin
  • Dystrophin-Associated Proteins
  • Hermanski-Pudlak Syndrome* / genetics
  • Hermanski-Pudlak Syndrome* / metabolism
  • Hermanski-Pudlak Syndrome* / physiopathology
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Melanocytes / metabolism
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Membrane Transport Proteins / genetics
  • Membrane Transport Proteins / metabolism
  • Mutation
  • Organelles / metabolism*
  • Proteins / genetics
  • Proteins / metabolism

Substances

  • AP3B1 protein, human
  • Adaptor Protein Complex 3
  • Adaptor Protein Complex beta Subunits
  • BLOC1S3 protein, human
  • Carrier Proteins
  • DTNBP1 protein, human
  • Dysbindin
  • Dystrophin-Associated Proteins
  • HPS1 protein, human
  • HPS3 protein, human
  • HPS4 protein, human
  • HPS5 protein, human
  • HPS6 protein, human
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • Membrane Transport Proteins
  • Proteins