A 14-3-3γ dimer-based scaffold bridges CtBP1-S/BARS to PI(4)KIIIβ to regulate post-Golgi carrier formation

Nat Cell Biol. 2012 Feb 26;14(4):343-54. doi: 10.1038/ncb2445.

Abstract

Large pleiomorphic carriers leave the Golgi complex for the plasma membrane by en bloc extrusion of specialized tubular domains, which then undergo fission. Several components of the underlying molecular machinery have been identified, including those involved in the budding/initiation of tubular carrier precursors (for example, the phosphoinositide kinase PI(4)KIIIβ, the GTPase ARF, and FAPP2), and in the fission of these precursors (for example, PKD, CtBP1-S/BARS). However, how these proteins interact to bring about carrier formation is poorly understood. Here, we describe a protein complex that mediates carrier formation and contains budding and fission molecules, as well as other molecules, such as the adaptor protein 14-3-3γ. Specifically, we show that 14-3-3γ dimers bridge CtBP1-S/BARS with PI(4)KIIIβ, and that the resulting complex is stabilized by phosphorylation by PKD and PAK. Disrupting the association of these proteins inhibits the fission of elongating carrier precursors, indicating that this complex couples the carrier budding and fission processes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 14-3-3 Proteins / metabolism*
  • Alcohol Oxidoreductases / metabolism*
  • Animals
  • COS Cells
  • Carrier Proteins / metabolism*
  • Chlorocebus aethiops
  • DNA-Binding Proteins / metabolism*
  • Dimerization
  • Golgi Apparatus / metabolism*
  • Humans
  • Phosphorylation
  • Phosphotransferases (Alcohol Group Acceptor) / metabolism*
  • Protein Kinase C / metabolism
  • Rats
  • p21-Activated Kinases / metabolism

Substances

  • 14-3-3 Proteins
  • Carrier Proteins
  • DNA-Binding Proteins
  • Alcohol Oxidoreductases
  • C-terminal binding protein
  • Phosphotransferases (Alcohol Group Acceptor)
  • 1-phosphatidylinositol-4-phosphate 5-kinase
  • protein kinase D
  • p21-Activated Kinases
  • Protein Kinase C