Drosophila PAR-1 and 14-3-3 Inhibit Bazooka/PAR-3 to Establish Complementary Cortical Domains in Polarized Cells

Cell. 2003 Dec 12;115(6):691-704. doi: 10.1016/s0092-8674(03)00938-3.

Abstract

PAR-1 kinases are required for polarity in diverse cell types, such as epithelial cells, where they localize laterally. PAR-1 activity is believed to be transduced by binding of 14-3-3 proteins to its phosphorylated substrates, but the relevant targets are unknown. We show that PAR-1 phosphorylates Bazooka/PAR-3 on two conserved serines to generate 14-3-3 binding sites. This inhibits formation of the Bazooka/PAR-6/aPKC complex by blocking Bazooka oligomerization and binding to aPKC. In epithelia, this complex localizes apically and defines the apical membrane, whereas Bazooka lacking PAR-1 phosphorylation/14-3-3 binding sites forms ectopic lateral complexes. Lateral exclusion by PAR-1/14-3-3 cooperates with apical anchoring by Crumbs/Stardust to restrict Bazooka localization, and loss of both pathways disrupts epithelial polarity. PAR-1 also excludes Bazooka from the posterior of the oocyte, and disruption of this regulation causes anterior-posterior polarity defects. Thus, antagonism of Bazooka by PAR-1/14-3-3 may represent a general mechanism for establishing complementary cortical domains in polarized cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 14-3-3 Proteins
  • Animals
  • Binding Sites / genetics
  • Body Patterning / genetics
  • Carrier Proteins / antagonists & inhibitors
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Differentiation / genetics
  • Cell Membrane / genetics
  • Cell Membrane / metabolism
  • Cell Polarity / physiology*
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / embryology*
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / metabolism
  • Epithelial Cells / cytology
  • Epithelial Cells / metabolism*
  • Glycogen Synthase Kinase 3
  • Intracellular Signaling Peptides and Proteins*
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Oocytes / cytology
  • Oocytes / growth & development
  • Oocytes / metabolism
  • Phosphorylation
  • Protein Binding / genetics
  • Protein Kinase C / genetics
  • Protein Kinase C / metabolism
  • Protein Kinases / genetics
  • Protein Kinases / metabolism*
  • Protein-Serine-Threonine Kinases
  • Tyrosine 3-Monooxygenase / genetics
  • Tyrosine 3-Monooxygenase / metabolism*

Substances

  • 14-3-3 Proteins
  • Carrier Proteins
  • Drosophila Proteins
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • baz protein, Drosophila
  • crb protein, Drosophila
  • Tyrosine 3-Monooxygenase
  • Protein Kinases
  • Protein-Serine-Threonine Kinases
  • PKC-3 protein
  • Protein Kinase C
  • Glycogen Synthase Kinase 3
  • Par-1 protein, Drosophila