Piezo1 forms a slowly-inactivating mechanosensory channel in mouse embryonic stem cells

  1. Josefina Inés del Mármol
  2. Kouki K Touhara
  3. Gist Croft
  4. Roderick MacKinnon  Is a corresponding author
  1. Howard Hughes Medical Institute, The Rockefeller University, United States

Abstract

Piezo1 is a mechanosensitive (MS) ion channel with characteristic fast-inactivation kinetics. We found a slowly-inactivating MS current in mouse embryonic stem (mES) cells and characterized it throughout their differentiation into motor-neurons to investigate its components. MS currents were large and slowly-inactivating in the stem-cell stage, and became smaller and faster-inactivating throughout the differentiation. We found that Piezo1 is expressed in mES cells, and its knockout abolishes MS currents, indicating that the slowly-inactivating current in mES cells is carried by Piezo1. To further investigate its slow inactivation in these cells, we cloned Piezo1 cDNA from mES cells and found that it displays fast-inactivation kinetics in heterologous expression, indicating that sources of modulation other than the aminoacid sequence determine its slow kinetics in mES cells. Finally, we report that Piezo1 knockout ES cells showed a reduced rate of proliferation but no significant differences in other markers of pluripotency and differentiation.

Data availability

Sequencing data have been deposited in GEO under accession number GSE106526. Source dat files have been provided for figures 1, 2, 4, 5, and 6, and source data for figure 7 is included as supporting file.

The following data sets were generated

Article and author information

Author details

  1. Josefina Inés del Mármol

    Laboratory of Molecular Neurobiology and Biophysics, Howard Hughes Medical Institute, The Rockefeller University, New York City, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Kouki K Touhara

    Laboratory of Molecular Neurobiology and Biophysics, Howard Hughes Medical Institute, The Rockefeller University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Gist Croft

    Laboratory of Molecular Neurobiology and Biophysics, Howard Hughes Medical Institute, The Rockefeller University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Roderick MacKinnon

    Laboratory of Molecular Neurobiology and Biophysics, Howard Hughes Medical Institute, The Rockefeller University, New York, United States
    For correspondence
    mackinn@mail.rockefeller.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7605-4679

Funding

Howard Hughes Medical Institute

  • Josefina Inés del Mármol
  • Roderick MacKinnon

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Copyright

© 2018, del Mármol 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

  • 3,829
    views
  • 659
    downloads
  • 71
    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)

  1. Josefina Inés del Mármol
  2. Kouki K Touhara
  3. Gist Croft
  4. Roderick MacKinnon
(2018)
Piezo1 forms a slowly-inactivating mechanosensory channel in mouse embryonic stem cells
eLife 7:e33149.
https://doi.org/10.7554/eLife.33149

Share this article

https://doi.org/10.7554/eLife.33149

Further reading

    1. Neuroscience
    Sara A Nolin, Mary E Faulkner ... Kristina Visscher
    Research Article

    The brain is organized into systems and networks of interacting components. The functional connections among these components give insight into the brain's organization and may underlie some cognitive effects of aging. Examining the relationship between individual differences in brain organization and cognitive function in older adults who have reached oldest old ages with healthy cognition can help us understand how these networks support healthy cognitive aging. We investigated functional network segregation in 146 cognitively healthy participants aged 85+ in the McKnight Brain Aging Registry. We found that the segregation of the association system and the individual networks within the association system [the fronto-parietal network (FPN), cingulo-opercular network (CON) and default mode network (DMN)], has strong associations with overall cognition and processing speed. We also provide a healthy oldest-old (85+) cortical parcellation that can be used in future work in this age group. This study shows that network segregation of the oldest-old brain is closely linked to cognitive performance. This work adds to the growing body of knowledge about differentiation in the aged brain by demonstrating that cognitive ability is associated with differentiated functional networks in very old individuals representing successful cognitive aging.

    1. Neuroscience
    Olga Kepinska, Josue Dalboni da Rocha ... Narly Golestani
    Research Article

    This study examines whether auditory cortex anatomy reflects multilingual experience, specifically individuals’ phonological repertoire. Using data from over 200 participants exposed to 1–7 languages across 36 languages, we analyzed the role of language experience and typological distances between languages they spoke in shaping neural signatures of multilingualism. Our findings reveal a negative relationship between the thickness of the left and right second transverse temporal gyrus (TTG) and participants’ degree of multilingualism. Models incorporating phoneme-level information in the language experience index explained the most variance in TTG thickness, suggesting that a more extensive and more phonologically diverse language experience is associated with thinner cortices in the second TTG. This pattern, consistent across two datasets, supports the idea of experience-driven pruning and neural efficiency. Our findings indicate that experience with typologically distant languages appear to impact the brain differently than those with similar languages. Moreover, they suggest that early auditory regions seem to represent phoneme-level cross-linguistic information, contrary to the most established models of language processing in the brain, which suggest that phonological processing happens in more lateral posterior superior temporal gyrus (STG) and superior temporal sulcus (STS).