AP-4, a novel protein complex related to clathrin adaptors

J Biol Chem. 1999 Mar 12;274(11):7278-85. doi: 10.1074/jbc.274.11.7278.

Abstract

Here we report the identification and characterization of AP-4, a novel protein complex related to the heterotetrameric AP-1, AP-2, and AP-3 adaptors that mediate protein sorting in the endocytic and late secretory pathways. The key to the identification of this complex was the cloning and sequencing of two widely expressed, mammalian cDNAs encoding new homologs of the adaptor beta and sigma subunits named beta4 and sigma4, respectively. An antibody to beta4 recognized in human cells an approximately 83-kDa polypeptide that exists in both soluble and membrane-associated forms. Gel filtration, sedimentation velocity, and immunoprecipitation experiments revealed that beta4 is a component of a multisubunit complex (AP-4) that also contains the sigma4 polypeptide and two additional adaptor subunit homologs named mu4 (mu-ARP2) and epsilon. Immunofluorescence analyses showed that AP-4 is associated with the trans-Golgi network or an adjacent structure and that this association is sensitive to the drug brefeldin A. We propose that, like the related AP-1, AP-2, and AP-3 complexes, AP-4 plays a role in signal-mediated trafficking of integral membrane proteins in mammalian cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Protein Complex alpha Subunits
  • Adaptor Proteins, Vesicular Transport
  • Amino Acid Sequence
  • Animals
  • Clathrin / chemistry*
  • DNA, Complementary
  • HeLa Cells
  • Humans
  • Membrane Proteins / chemistry*
  • Mice
  • Microscopy, Fluorescence
  • Molecular Sequence Data
  • Monomeric Clathrin Assembly Proteins*
  • Nerve Tissue Proteins / chemistry*
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Phosphoproteins / chemistry*
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism
  • Sequence Homology, Amino Acid
  • Subcellular Fractions / chemistry

Substances

  • Adaptor Protein Complex alpha Subunits
  • Adaptor Proteins, Vesicular Transport
  • Clathrin
  • DNA, Complementary
  • Membrane Proteins
  • Monomeric Clathrin Assembly Proteins
  • Nerve Tissue Proteins
  • Phosphoproteins
  • clathrin assembly protein AP180

Associated data

  • GENBANK/AF092093
  • GENBANK/AF092094