Mechanical stretch scales centriole number to apical area via Piezo1 in multiciliated cells

  1. Saurabh Suhas Kulkarni  Is a corresponding author
  2. Jonathan Marquez
  3. Priya P Date
  4. Rosa Ventrella
  5. Brian Mitchell
  6. Mustafa Khokha  Is a corresponding author
  1. University of Virginia, United States
  2. Yale University, United States
  3. Northwestern University, United States
  4. 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

  1. Saurabh Suhas Kulkarni

    Cell Biology, University of Virginia, Charlottesville, United States
    For correspondence
    sk4xq@virginia.edu
    Competing interests
    No competing interests declared.
  2. Jonathan Marquez

    Yale School of Medicine, Yale University, New Haven, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3377-7599
  3. Priya P Date

    Cell Biology, University of Virginia, Charlottesville, United States
    Competing interests
    No competing interests declared.
  4. Rosa Ventrella

    Department of Cell and Developmental Biology, Northwestern University, Chicago, United States
    Competing interests
    No competing interests declared.
  5. Brian Mitchell

    Department of Cell and Developmental Biology, Northwestern University, Chicago, United States
    Competing interests
    No competing interests declared.
  6. Mustafa Khokha

    Pediatrics, Yale School of Medicine, New Haven, United States
    For correspondence
    Mustafa.khokha@yale.edu
    Competing interests
    Mustafa Khokha, is a founder of Victory Genomics.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9846-7076

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).

Reviewing Editor

  1. Jeremy F Reiter, University of California, San Francisco, United States

Publication history

  1. Received: December 30, 2020
  2. Accepted: June 28, 2021
  3. Accepted Manuscript published: June 29, 2021 (version 1)
  4. Version of Record published: July 9, 2021 (version 2)

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.

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  1. Saurabh Suhas Kulkarni
  2. Jonathan Marquez
  3. Priya P Date
  4. Rosa Ventrella
  5. Brian Mitchell
  6. Mustafa Khokha
(2021)
Mechanical stretch scales centriole number to apical area via Piezo1 in multiciliated cells
eLife 10:e66076.
https://doi.org/10.7554/eLife.66076
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