TY - JOUR
T1 - Dual-color live imaging unveils stepwise organization of multiple basal body arrays by cytoskeletons
AU - Shiratsuchi, Gen
AU - Konishi, Satoshi
AU - Yano, Tomoki
AU - Yanagihashi, Yuichi
AU - Nakayama, Shogo
AU - Katsuno, Tatsuya
AU - Kashihara, Hiroka
AU - Tanaka, Hiroo
AU - Tsukita, Kazuto
AU - Suzuki, Koya
AU - Herawati, Elisa
AU - Watanabe, Hitomi
AU - Hirai, Toyohiro
AU - Yagi, Takeshi
AU - Kondoh, Gen
AU - Gotoh, Shimpei
AU - Tamura, Atsushi
AU - Tsukita, Sachiko
N1 - Publisher Copyright:
© The Author(s) 2024.
PY - 2024/3/12
Y1 - 2024/3/12
N2 - For mucociliary clearance of pathogens, tracheal multiciliated epithelial cells (MCCs) organize coordinated beating of cilia, which originate from basal bodies (BBs) with basal feet (BFs) on one side. To clarify the self-organizing mechanism of coordinated intracellular BB-arrays composed of a well-ordered BB-alignment and unidirectional BB-orientation, determined by the direction of BB to BF, we generated double transgenic mice with GFP-centrin2-labeled BBs and mRuby3-Cep128-labeled BFs for long-term, high-resolution, dual-color live-cell imaging in primary-cultured tracheal MCCs. At early timepoints of MCC differentiation, BB-orientation and BB-local alignment antecedently coordinated in an apical microtubule-dependent manner. Later during MCC differentiation, fluctuations in BB-orientation were restricted, and locally aligned BB-arrays were further coordinated to align across the entire cell (BB-global alignment), mainly in an apical intermediate-sized filament-lattice-dependent manner. Thus, the high coordination of the BB-array was established for efficient mucociliary clearance as the primary defense against pathogen infection, identifying apical cytoskeletons as potential therapeutic targets.
AB - For mucociliary clearance of pathogens, tracheal multiciliated epithelial cells (MCCs) organize coordinated beating of cilia, which originate from basal bodies (BBs) with basal feet (BFs) on one side. To clarify the self-organizing mechanism of coordinated intracellular BB-arrays composed of a well-ordered BB-alignment and unidirectional BB-orientation, determined by the direction of BB to BF, we generated double transgenic mice with GFP-centrin2-labeled BBs and mRuby3-Cep128-labeled BFs for long-term, high-resolution, dual-color live-cell imaging in primary-cultured tracheal MCCs. At early timepoints of MCC differentiation, BB-orientation and BB-local alignment antecedently coordinated in an apical microtubule-dependent manner. Later during MCC differentiation, fluctuations in BB-orientation were restricted, and locally aligned BB-arrays were further coordinated to align across the entire cell (BB-global alignment), mainly in an apical intermediate-sized filament-lattice-dependent manner. Thus, the high coordination of the BB-array was established for efficient mucociliary clearance as the primary defense against pathogen infection, identifying apical cytoskeletons as potential therapeutic targets.
KW - Apical Cytoskeletons
KW - Ciliary Basal Bodies
KW - Coordinated Ciliary Beating
KW - Mucociliary Clearance
KW - Multiciliated Cells
UR - http://www.scopus.com/inward/record.url?scp=85185316637&partnerID=8YFLogxK
U2 - 10.1038/s44319-024-00066-0
DO - 10.1038/s44319-024-00066-0
M3 - 記事
C2 - 38316902
AN - SCOPUS:85185316637
SN - 1469-221X
VL - 25
SP - 1176
EP - 1207
JO - EMBO Reports
JF - EMBO Reports
IS - 3
ER -