PACS-1 defines a novel gene family of cytosolic sorting proteins required for trans-Golgi network localization

Cell. 1998 Jul 24;94(2):205-16. doi: 10.1016/s0092-8674(00)81420-8.


We report the role of one member of a novel gene family, PACS-1, in the localization of trans-Golgi network (TGN) membrane proteins. PACS-1 directs the TGN localization of furin by binding to the protease's phosphorylated cytosolic domain. Antisense studies show TGN localization of furin and mannose-6-phosphate receptor, but not TGN46, is strictly dependent on PACS-1. Analyses in vitro and in vivo show PACS-1 has properties of a coat protein and connects furin to components of the clathrin-sorting machinery. Cell-free assays indicate TGN localization of furin is directed by a PACS-1-mediated retrieval step. Together, these findings explain a mechanism by which membrane proteins in mammalian cells are localized to the TGN.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adaptor Protein Complex alpha Subunits
  • Adaptor Proteins, Vesicular Transport
  • Amino Acid Sequence
  • Animals
  • Capsid / genetics
  • Capsid / metabolism*
  • Carrier Proteins*
  • Cell Line
  • Clathrin / metabolism
  • Cloning, Molecular
  • Cytosol / metabolism
  • Furin
  • Golgi Apparatus / metabolism*
  • Membrane Proteins / metabolism*
  • Mice
  • Molecular Sequence Data
  • Multigene Family / genetics*
  • Phosphorylation
  • Receptor, IGF Type 2 / metabolism
  • Subtilisins / metabolism
  • Vesicular Transport Proteins


  • Adaptor Protein Complex alpha Subunits
  • Adaptor Proteins, Vesicular Transport
  • Carrier Proteins
  • Clathrin
  • Membrane Proteins
  • Pacs1 protein, mouse
  • Receptor, IGF Type 2
  • Vesicular Transport Proteins
  • Subtilisins
  • Furin

Associated data

  • GENBANK/AF076183
  • GENBANK/AF076184