Adaptor protein 3-dependent microtubule-mediated movement of lytic granules to the immunological synapse

Nat Immunol. 2003 Nov;4(11):1111-20. doi: 10.1038/ni1000. Epub 2003 Oct 19.


Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive disease characterized by platelet defects and oculocutaneous albinism. Individuals with HPS type 2 (HPS2) lack the cytosolic adaptor protein 3 (AP-3) involved in lysosomal sorting, and are also immunodeficient. Here we characterize an HPS2 mutation and demonstrate that AP-3 deficiency leads to a loss of cytotoxic T lymphocyte (CTL)-mediated cytotoxicity. Although the lysosomal protein CD63 was mislocalized to the plasma membrane, perforin and granzymes were correctly localized to the lytic granules in AP-3-deficient CTLs. However, the lytic granules of AP-3-deficient CTLs were enlarged and were unable to move along microtubules and dock within the secretory domain of the immunological synapse. These data show that AP-3 is essential for polarized secretion from CTLs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Protein Complex 3 / deficiency
  • Adaptor Protein Complex 3 / genetics
  • Adaptor Protein Complex 3 / metabolism*
  • Adaptor Protein Complex beta Subunits
  • Antigens, CD / metabolism
  • Base Sequence
  • Cytoplasmic Granules / metabolism*
  • Cytoplasmic Granules / ultrastructure
  • Hermanski-Pudlak Syndrome / metabolism
  • Humans
  • Immune System / immunology
  • Immune System / metabolism*
  • Membrane Transport Proteins*
  • Microtubules / metabolism*
  • Molecular Sequence Data
  • Mutation
  • Platelet Membrane Glycoproteins / metabolism
  • Proteins / metabolism
  • T-Lymphocytes, Cytotoxic / metabolism
  • T-Lymphocytes, Cytotoxic / ultrastructure
  • Tetraspanin 30


  • AP3B1 protein, human
  • Adaptor Protein Complex 3
  • Adaptor Protein Complex beta Subunits
  • Antigens, CD
  • CD63 protein, human
  • Membrane Transport Proteins
  • Platelet Membrane Glycoproteins
  • Proteins
  • Tetraspanin 30

Associated data

  • RefSeq/NT_006713