Membrane targeting of Bazooka/PAR-3 is mediated by direct binding to phosphoinositide lipids

Curr Biol. 2010 Apr 13;20(7):636-42. doi: 10.1016/j.cub.2010.01.065. Epub 2010 Mar 18.

Abstract

Cell polarity in higher animals is controlled by evolutionarily conserved protein complexes, which localize to the cytocortex in a polarized manner. The PAR-3/PAR-6/atypical protein kinase C (aPKC) complex is the first to become asymmetrically localized, and it controls the localization of additional complexes functioning further downstream in the regulation of cell polarity. The first component of the PAR-3/PAR-6/aPKC complex that is localized to the cortex is Bazooka/PAR-3 (Baz), a large scaffolding protein. In most cell types analyzed, loss of Baz function leads to loss of cell polarity. Here we present a structure-function analysis of Baz focusing on its subcellular localization and function in four different polarized Drosophila cell types: the embryonic ectodermal epidermis, the follicular epithelium, embryonic neuroblasts, and the oocyte. We show that the PDZ domains of Baz are dispensable for its correct localization, whereas a conserved region in the C-terminal part of Baz to which no function had been assigned so far is required and sufficient for membrane localization. This region binds to phosphoinositide membrane lipids and thus mediates cortical localization of Baz by direct interaction with the plasma membrane. Our findings reveal a mechanism for the coupling of plasma membrane polarity and cortical polarity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Animals, Genetically Modified
  • Binding Sites
  • Cell Membrane / metabolism
  • Cell Polarity
  • Drosophila / cytology
  • Drosophila / embryology
  • Drosophila / genetics
  • Drosophila / metabolism*
  • Drosophila Proteins / chemistry
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Female
  • Genes, Insect
  • Intracellular Signaling Peptides and Proteins / chemistry
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Molecular Sequence Data
  • Mutation
  • Neurons / metabolism
  • Oocytes / metabolism
  • Peptide Fragments / chemistry
  • Peptide Fragments / genetics
  • Peptide Fragments / metabolism
  • Phosphatidylinositols / metabolism*
  • Protein Binding
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Sequence Deletion
  • Sequence Homology, Amino Acid

Substances

  • Drosophila Proteins
  • Intracellular Signaling Peptides and Proteins
  • Peptide Fragments
  • Phosphatidylinositols
  • Recombinant Fusion Proteins
  • baz protein, Drosophila