PAR3 and aPKC regulate Golgi organization through CLASP2 phosphorylation to generate cell polarity

Mol Biol Cell. 2015 Feb 15;26(4):751-61. doi: 10.1091/mbc.E14-09-1382. Epub 2014 Dec 17.

Abstract

The organization of the Golgi apparatus is essential for cell polarization and its maintenance. The polarity regulator PAR complex (PAR3, PAR6, and aPKC) plays critical roles in several processes of cell polarization. However, how the PAR complex participates in regulating the organization of the Golgi remains largely unknown. Here we demonstrate the functional cross-talk of the PAR complex with CLASP2, which is a microtubule plus-end-tracking protein and is involved in organizing the Golgi ribbon. CLASP2 directly interacted with PAR3 and was phosphorylated by aPKC. In epithelial cells, knockdown of either PAR3 or aPKC induced the aberrant accumulation of CLASP2 at the trans-Golgi network (TGN) concomitantly with disruption of the Golgi ribbon organization. The expression of a CLASP2 mutant that inhibited the PAR3-CLASP2 interaction disrupted the organization of the Golgi ribbon. CLASP2 is known to localize to the TGN through its interaction with the TGN protein GCC185. This interaction was inhibited by the aPKC-mediated phosphorylation of CLASP2. Furthermore, the nonphosphorylatable mutant enhanced the colocalization of CLASP2 with GCC185, thereby perturbing the Golgi organization. On the basis of these observations, we propose that PAR3 and aPKC control the organization of the Golgi through CLASP2 phosphorylation.

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Cell Cycle Proteins / physiology*
  • Cell Polarity*
  • Epithelial Cells / metabolism
  • Golgi Apparatus / metabolism*
  • Golgi Apparatus / ultrastructure
  • Humans
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Membrane Proteins / physiology*
  • Microtubule-Associated Proteins / metabolism*
  • Microtubules / metabolism
  • Microtubules / ultrastructure
  • Phosphorylation
  • Protein Kinase C / genetics
  • Protein Kinase C / metabolism
  • Protein Kinase C / physiology*
  • trans-Golgi Network / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • CLASP2 protein, human
  • Cell Cycle Proteins
  • Membrane Proteins
  • Microtubule-Associated Proteins
  • PARD3 protein, human
  • PKC-3 protein
  • Protein Kinase C