Mechanical stretch scales centriole number to apical area via Piezo1 in multiciliated cells
- University of Virginia, United States
- Yale University, United States
- Northwestern University, United States
- Yale School of Medicine, United States
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.
Data availability
Data is attached as a source files.
Article and author information
Author details
Funding
NHLBI (1K99 HL133606 and 5R00HL133606)
- Saurabh Suhas Kulkarni
NICHD (R01HD102186)
- Mustafa Khokha
Yale MSTP NIH (T32GM007205)
- Jonathan Marquez
Yale Predoctoral Program in cellular and Molecular Biology (T32GM007223)
- Jonathan Marquez
Paul and Daisy Soros Fellowship for New Americans
- Jonathan Marquez
NIH (T32AR060710)
- Rosa Ventrella
NIGMS (R01GM089970)
- Brian Mitchell
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: Xenopus tropicalis were housed and cared for in our aquatics facility according to established protocols approved by the Yale Institutional Animal Care and Use Committee (IACUC, protocol number - 2021-11035) and University of Virginia IACUC (protocol number - 42951119). Xenopus laevis were housed and cared for according to established animal care protocol approved by Northwestern University IACUC (protocol number - IS00006468).
Copyright
© 2021, Kulkarni et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 4,153
- views
-
- 490
- downloads
-
- 25
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Mechanical stretch scales centriole number to apical area via Piezo1 in multiciliated cells
eLife 10:e66076.
https://doi.org/10.7554/eLife.66076
