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A polarity complex of mPar-6 and atypical PKC binds, phosphorylates and regulates mammalian Lgl

Pamela J Plant1, James P Fawcett, Dan C C Lin

  • 1Programme in Molecular Biology and Cancer, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto M5G 1X5 Canada.

Nature Cell Biology
|March 12, 2003
PubMed

Insights

This study reveals how atypical protein kinase C (aPKC) interacts with mPar-6C and Mlgl to regulate cell polarity. Phosphorylation of Mlgl by aPKC is crucial for cell polarization and protein trafficking.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Developmental Biology

Background:

  • Cell polarity and asymmetric cell division are regulated by conserved protein complexes.
  • Downstream targets of the Par-6/aPKC/Cdc42/Par-3 complex remain largely uncharacterized.

Purpose of the Study:

  • To identify direct physiological interactions and regulatory mechanisms involving mammalian aPKC, mPar-6C, and Mlgl.
  • To elucidate the role of Mlgl phosphorylation in cell polarization and protein trafficking.

Main Methods:

  • Co-immunoprecipitation assays to detect protein complex formation.
  • In vitro kinase assays to identify phosphorylation sites.
  • Cell culture and wound-healing assays in mouse embryonic fibroblasts.
  • Analysis of protein localization in cultured cells and mouse brain.

Main Results:

  • Mammalian aPKC, mPar-6C, and Mlgl form a stable multiprotein complex.
  • aPKC phosphorylates Mlgl on conserved serine residues.
  • Mlgl phosphorylation is essential for proper cell polarization during wound response.
  • This interaction influences Mlgl's role in protein trafficking.

Conclusions:

  • Mlgl is a direct functional substrate of aPKC in the context of cell polarization.
  • aPKC is recruited to polarity substrates via interactions with proteins like mPar-6C and Mlgl.
  • This study establishes a physical and regulatory link between distinct cell polarity complexes.

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