CAMSAP3 orients the apical-to-basal polarity of microtubule arrays in epithelial cells.

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  • Additional Information
    • Source:
      Publisher: National Academy of Sciences Country of Publication: United States NLM ID: 7505876 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1091-6490 (Electronic) Linking ISSN: 00278424 NLM ISO Abbreviation: Proc Natl Acad Sci U S A Subsets: MEDLINE
    • Publication Information:
      Original Publication: Washington, DC : National Academy of Sciences
    • Subject Terms:
      Cell Polarity*; Epithelial Cells/*cytology ; Epithelial Cells/*metabolism ; Microtubule-Associated Proteins/*metabolism ; Microtubules/*metabolism ; Organelles/*metabolism; Amino Acid Sequence ; Animals ; Bridged Bicyclo Compounds, Heterocyclic/pharmacology ; Caco-2 Cells ; Enterocytes/cytology ; Enterocytes/metabolism ; Enterocytes/ultrastructure ; Epithelial Cells/ultrastructure ; Green Fluorescent Proteins/metabolism ; Homozygote ; Humans ; Mice, Inbred C57BL ; Mice, Mutant Strains ; Microtubule-Associated Proteins/chemistry ; Models, Biological ; Molecular Sequence Data ; Mutation/genetics ; Nocodazole/pharmacology ; Protein Structure, Tertiary ; Subcellular Fractions/metabolism ; Thiazolidines/pharmacology
    • Abstract:
      Polarized epithelial cells exhibit a characteristic array of microtubules that are oriented along the apicobasal axis of the cells. The minus-ends of these microtubules face apically, and the plus-ends face toward the basal side. The mechanisms underlying this epithelial-specific microtubule assembly remain unresolved, however. Here, using mouse intestinal cells and human Caco-2 cells, we show that the microtubule minus-end binding protein CAMSAP3 (calmodulin-regulated-spectrin-associated protein 3) plays a pivotal role in orienting the apical-to-basal polarity of microtubules in epithelial cells. In these cells, CAMSAP3 accumulated at the apical cortices, and tethered the longitudinal microtubules to these sites. Camsap3 mutation or depletion resulted in a random orientation of these microtubules; concomitantly, the stereotypic positioning of the nucleus and Golgi apparatus was perturbed. In contrast, the integrity of the plasma membrane was hardly affected, although its structural stability was decreased. Further analysis revealed that the CC1 domain of CAMSAP3 is crucial for its apical localization, and that forced mislocalization of CAMSAP3 disturbs the epithelial architecture. These findings demonstrate that apically localized CAMSAP3 determines the proper orientation of microtubules, and in turn that of organelles, in mature mammalian epithelial cells.
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    • Contributed Indexing:
      Keywords: CAMSAP; Nezha; intestinal epithelial cell; microtubule assembly; microtubule minus-end
    • Accession Number:
      0 (Bridged Bicyclo Compounds, Heterocyclic)
      0 (Camsap3 protein, human)
      0 (Camsap3 protein, mouse)
      0 (Microtubule-Associated Proteins)
      0 (Thiazolidines)
      147336-22-9 (Green Fluorescent Proteins)
      SH1WY3R615 (Nocodazole)
      SRQ9WWM084 (latrunculin A)
    • Publication Date:
      Date Created: 20151231 Date Completed: 20160614 Latest Revision: 20181113
    • Publication Date:
      20240829
    • Accession Number:
      PMC4720291
    • Accession Number:
      10.1073/pnas.1520638113
    • Accession Number:
      26715742