TY - JOUR
T1 - Cyst formation in proximal renal tubules caused by dysfunction of the microtubule minus-end regulator CAMSAP3
AU - Mitsuhata, Yuto
AU - Abe, Takaya
AU - Misaki, Kazuyo
AU - Nakajima, Yuna
AU - Kiriya, Keita
AU - Kawasaki, Miwa
AU - Kiyonari, Hiroshi
AU - Takeichi, Masatoshi
AU - Toya, Mika
AU - Sato, Masamitsu
N1 - Funding Information:
We thank M. Takasato for discussions, suggestions and critical reading of the manuscript, M. Yanagita for discussions and suggestions, and Y. Okada for discussions, suggestions and technical support for laser scanning microscopy. Some of the imaging experiments were performed at the RIKEN Kobe Imaging Facility. This work was supported by JSPS KAKENHI Grant Numbers JP25221104 to M. Takeichi, JP16H0407, JP16H0317, and JP18K19347 to M. Sato, and JP25440094, JP17K07397, and JP20K06645 to M. Toya. Support also came from Daiichi Sankyo Foundation of Life Science and Waseda University grants for Special Research Projects Grant Numbers 2018B-222, 2019C-570, and 2020R-038 to M. S. and 2018S-139 and 2019C-571 to M. Toya.
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
N2 - 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.
AB - 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.
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U2 - 10.1038/s41598-021-85416-x
DO - 10.1038/s41598-021-85416-x
M3 - Article
C2 - 33712686
AN - SCOPUS:85102502920
SN - 2045-2322
VL - 11
JO - Scientific reports
JF - Scientific reports
IS - 1
M1 - 5857
ER -