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The Par3-like polarity protein Par3L is essential for mammary stem cell maintenance.

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  • Author(s): Huo Y;Huo Y; Macara IG; Macara IG
  • Source:
    Nature cell biology [Nat Cell Biol] 2014 Jun; Vol. 16 (6), pp. 529-37. Date of Electronic Publication: 2014 May 25.
  • Publication Type:
    Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: Macmillan Magazines Ltd Country of Publication: England NLM ID: 100890575 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1476-4679 (Electronic) Linking ISSN: 14657392 NLM ISO Abbreviation: Nat Cell Biol Subsets: MEDLINE
    • Publication Information:
      Original Publication: London : Macmillan Magazines Ltd., [1999-
    • Subject Terms:
      Cell Polarity* ; Signal Transduction*; Intracellular Signaling Peptides and Proteins/*metabolism ; Mammary Glands, Animal/*metabolism ; Multipotent Stem Cells/*metabolism; AMP-Activated Protein Kinases ; Adaptor Proteins, Signal Transducing ; Animals ; Apoptosis ; Cell Adhesion Molecules/metabolism ; Cell Cycle Proteins ; Cell Differentiation ; Cell Proliferation ; Cell Survival ; Cells, Cultured ; Female ; Intracellular Signaling Peptides and Proteins/genetics ; Keratin-8/metabolism ; Mammary Glands, Animal/pathology ; Mice ; Mice, Inbred C3H ; Multipotent Stem Cells/pathology ; Multipotent Stem Cells/transplantation ; Protein Binding ; Protein Serine-Threonine Kinases/metabolism ; RNA Interference ; Tight Junctions/metabolism ; Transfection
    • Abstract:
      The Par polarity proteins play key roles in asymmetric division of Drosophila melanogaster stem cells; however, whether the same mechanisms control stem cells in mammals is controversial. Although necessary for mammary gland morphogenesis, Par3 is not essential for mammary stem cell function. We discovered that, instead, a previously uncharacterized protein, Par3-like (Par3L), is vital for mammary gland stem cell maintenance. Par3L function has been mysterious because, unlike Par3, it does not interact with atypical protein kinase C or the Par6 polarity protein. We found that Par3L is expressed by multipotent stem cells in the terminal end buds of murine mammary glands. Ablation of Par3L resulted in rapid and profound stem cell loss. Unexpectedly, Par3L, but not Par3, binds to the tumour suppressor protein Lkb1 and inhibits its kinase activity. This interaction is key for the function of Par3L in mammary stem cell maintenance. Our data reveal insights into a link between cell polarity proteins and stem cell survival, and uncover a biological function for Par3L.
    • Comments:
      Erratum in: Nat Cell Biol. 2014 Jul;16(7):716.
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    • Grant Information:
      R01 GM070902 United States GM NIGMS NIH HHS; GM070902 United States GM NIGMS NIH HHS
    • Accession Number:
      0 (Adaptor Proteins, Signal Transducing)
      0 (Cell Adhesion Molecules)
      0 (Cell Cycle Proteins)
      0 (Intracellular Signaling Peptides and Proteins)
      0 (Keratin-8)
      0 (Krt8 protein, mouse)
      0 (Par3L protein, mouse)
      0 (Pard3 protein, mouse)
      EC 2.7.11.1 (Protein Serine-Threonine Kinases)
      EC 2.7.11.1 (Stk11 protein, mouse)
      EC 2.7.11.31 (AMP-Activated Protein Kinases)
    • Publication Date:
      Date Created: 20140527 Date Completed: 20140729 Latest Revision: 20211203
    • Publication Date:
      20250114
    • Accession Number:
      PMC4083567
    • Accession Number:
      10.1038/ncb2969
    • Accession Number:
      24859006