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

Mika Toya, Saeko Kobayashi, Miwa Kawasaki, Go Shioi, Mari Kaneko, Takashi Ishiuchi, Kazuyo Misaki, Wenxiang Meng, Masatoshi Takeichi

Research output: Contribution to journalArticle

53 Citations (Scopus)

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 epithelialspecific microtubule assembly remain unresolved, however. Here, using mouse intestinal cells and human Caco-2 cells, we show that themicrotubuleminus-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, inmature mammalian epithelial cells.

Original languageEnglish
Pages (from-to)332-337
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume113
Issue number2
DOIs
Publication statusPublished - 2016 Jan 12

Keywords

  • CAMSAP
  • Intestinal epithelial cell
  • Microtubule assembly
  • Microtubule minus-end
  • Nezha

ASJC Scopus subject areas

  • General

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