Cyst formation in proximal renal tubules caused by dysfunction of the microtubule minus-end regulator CAMSAP3

Yuto Mitsuhata, Takaya Abe, Kazuyo Misaki, Yuna Nakajima, Keita Kiriya, Miwa Kawasaki, Hiroshi Kiyonari, Masatoshi Takeichi, Mika Toya*, Masamitsu Sato

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Epithelial cells organize an ordered array of non-centrosomal microtubules, the minus ends of which are regulated by CAMSAP3. The role of these microtubules in epithelial functions, however, is poorly understood. Here, we show that the kidneys of mice in which Camsap3 is mutated develop cysts at the proximal convoluted tubules (PCTs). PCTs were severely dilated in the mutant kidneys, and they also exhibited enhanced cell proliferation. In these PCTs, epithelial cells became flattened along with perturbation of microtubule arrays as well as of certain subcellular structures such as interdigitating basal processes. Furthermore, YAP and PIEZO1, which are known as mechanosensitive regulators for cell shaping and proliferation, were activated in these mutant PCT cells. These observations suggest that CAMSAP3-mediated microtubule networks are important for maintaining the proper mechanical properties of PCT cells, and its loss triggers cell deformation and proliferation via activation of mechanosensors, resulting in the dilation of PCTs.

Original languageEnglish
Article number5857
JournalScientific reports
Volume11
Issue number1
DOIs
Publication statusPublished - 2021 Dec

ASJC Scopus subject areas

  • General

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