@article{4aa2c1324db6495c9e1fa2373db0f192,
title = "Mechanical stretch scales centriole number to apical area via piezo1 in multiciliated cells",
abstract = "How cells count and regulate organelle number is a fundamental question in cell biology. For example, most cells restrict centrioles to two in number and assemble one cilium; however, multiciliated cells (MCCs) synthesize hundreds of centrioles to assemble multiple cilia. Aberration in centriole/cilia number impairs MCC function and can lead to pathological outcomes. Yet how MCCs control centriole number remains unknown. Using Xenopus, we demonstrate that centriole number scales with apical area over a remarkable 40-fold change in size. We find that tensile forces that shape the apical area also trigger centriole amplification based on both cell stretching experiments and disruption of embryonic elongation. Unexpectedly, Piezo1, a mechanosensitive ion channel, localizes near each centriole suggesting a potential role in centriole amplification. Indeed, depletion of Piezo1 affects centriole amplification and disrupts its correlation with the apical area in a tension dependent manner. Thus, mechanical forces calibrate cilia/centriole number to the MCC apical area via Piezo1. Our results provide new perspectives to study organelle number control essential for optimal cell function.",
author = "Saurabh Kulkarni and Jonathan Marquez and Priya Date and Rosa Ventrella and Mitchell, {Brian J.} and Khokha, {Mustafa K.}",
note = "Funding Information: was supported by the Yale MSTP NIH T32GM007205 Training grant, the Yale Funding Information: We would like to thank Doug Desimone and Patrick Lusk for discussions and their valuable comments on the paper, Lance Davidson for his valuable input on animal cap and mechanical stretching experiments, and Ellen Su at the Yale Tsai Center for Innovative Thinking for guidance on developing the stretch apparatus used in this work. We would also like to thank the Yale Center for Engineering Innovation and Design for use of instruments in the production of the custom stretch apparatus. We thank the Yale Center for Advanced Light Microscopy for their assistance with confocal imaging. S.S.K. was supported by the NIH Pathway to Independence K99/R00 grant (1K99 HL133606 and 5R00HL133606). M.K.K. was supported by the NIH/NICHD (R01HD102186). J.M. was supported by the Yale MSTP NIH T32GM007205 Training grant, the Yale Predoctoral Program in cellular and Molecular Biology T32GM007223 Training Grant, and the Paul and Daisy Soros Fellowship for New Americans. RV was supported by a T32 Training grant in Cutaneous Biology (T32AR060710). BJM was supported by NIH/NIGMS (R01GM089970). Funding Information: and 5R00HL133606). M.K.K. was supported by the NIH/NICHD (R01HD102186). J.M. Funding Information: was supported by the NIH Pathway to Independence K99/R00 grant (1K99 HL133606 Funding Information: and the Paul and Daisy Soros Fellowship for New Americans. RV was supported by a Publisher Copyright: {\textcopyright} 2021, eLife Sciences Publications Ltd. All rights reserved.",
year = "2021",
month = jun,
doi = "10.7554/eLife.66076",
language = "English (US)",
volume = "10",
journal = "eLife",
issn = "2050-084X",
publisher = "eLife Sciences Publications",
}