1. Neuroscience
  2. Structural Biology and Molecular Biophysics
Download icon

Dynamic change of electrostatic field in TMEM16F permeation pathway shifts its ion selectivity

  1. Wenlei Ye
  2. Tina W Han
  3. Mu He
  4. Yuh Nung Jan
  5. Lily Yeh Jan  Is a corresponding author
  1. Howard Hughes Medical Institute, University of California, San Francisco, United States
Research Article
  • Cited 3
  • Views 1,952
  • Annotations
Cite this article as: eLife 2019;8:e45187 doi: 10.7554/eLife.45187

Abstract

TMEM16F is activated by elevated intracellular Ca2+, and functions as a small-conductance ion channel and as a phospholipid scramblase. In contrast to its paralogs, the TMEM16A/B calcium-activated chloride channels, mouse TMEM16F has been reported as a cation-, anion-, or non-selective ion channel, without a definite conclusion. Starting with the Q559K mutant that shows no current rundown and less outward rectification in excised patch, we found that the channel shifted its ion selectivity in response to the change of intracellular Ca2+ concentration, with an increased permeability ratio of Cl- to Na+ (PCl-/PNa+) at a higher Ca2+ level. The gradual shift of relative ion permeability did not correlate with the channel activation state. Instead, it was indicative of an alteration of electrostatic field in the permeation pathway. The dynamic change of ion selectivity suggests a charge-screening mechanism for TMEM16F ion conduction, and it provides hints to the study of TMEM16F physiological functions.

Article and author information

Author details

  1. Wenlei Ye

    Department of Physiology, Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4694-1493

  2. Tina W Han

    Department of Physiology, Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.

  3. Mu He

    Department of Physiology, Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.

  4. Yuh Nung Jan

    Department of Physiology, Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1367-6299

  5. Lily Yeh Jan

    Department of Physiology, Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, United States
    For correspondence
    Lily.Jan@ucsf.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3938-8498

Funding

National Institute of Neurological Disorders and Stroke (R01NS069229)

  • Lily Yeh Jan

Jane Coffin Childs Memorial Fund for Medical Research

  • Tina W Han

Eunice Kennedy Shriver National Institute of Child Health and Human Development (F32HD089639)

  • Mu He

Howard Hughes Medical Institute

  • Yuh Nung Jan
  • Lily Yeh Jan

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

Reviewing Editor

  1. Kenton Jon Swartz, National Institute of Neurological Disorders and Stroke, National Institutes of Health, United States

Publication history

  1. Received: January 14, 2019
  2. Accepted: July 17, 2019
  3. Accepted Manuscript published: July 18, 2019 (version 1)
  4. Version of Record published: August 12, 2019 (version 2)

Copyright

© 2019, Ye 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

  • 1,952
    Page views
  • 364
    Downloads
  • 3
    Citations

Article citation count generated by polling the highest count across the following sources: PubMed Central, Crossref, Scopus.

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)

Download citations (links to download the citations from this article in formats compatible with various reference manager tools)

Open citations (links to open the citations from this article in various online reference manager services)

Categories and tags

Research organism

Further reading

    1. Neuroscience

    Amplitude modulations of cortical sensory responses in pulsatile evidence accumulation

    Sue Ann Koay et al.
    Research Article Updated

    How does the brain internally represent a sequence of sensory information that jointly drives a decision-making behavior? Studies of perceptual decision-making have often assumed that sensory cortices provide noisy but otherwise veridical sensory inputs to downstream processes that accumulate and drive decisions. However, sensory processing in even the earliest sensory cortices can be systematically modified by various external and internal contexts. We recorded from neuronal populations across posterior cortex as mice performed a navigational decision-making task based on accumulating randomly timed pulses of visual evidence. Even in V1, only a small fraction of active neurons had sensory-like responses time-locked to each pulse. Here, we focus on how these ‘cue-locked’ neurons exhibited a variety of amplitude modulations from sensory to cognitive, notably by choice and accumulated evidence. These task-related modulations affected a large fraction of cue-locked neurons across posterior cortex, suggesting that future models of behavior should account for such influences.

    1. Neuroscience

    Brain functional networks associated with social bonding in monogamous voles

    María Fernanda López-Gutiérrez et al.
    Research Article

    Previous studies have related pair bonding in Microtus ochrogaster, the prairie vole, with plastic changes in several brain regions. However, the interactions between these socially-relevant regions have yet to be described. In this study, we used resting state magnetic resonance imaging to explore bonding behaviors and functional connectivity of brain regions previously associated with pair bonding. Thirty-two male and female prairie voles were scanned at baseline, 24h and 2 weeks after the onset of cohabitation By using network based statistics, we identified that the functional connectivity of a cortico-striatal network predicted the onset of affiliative behavior, while another predicted the amount of social interaction during a partner preference test. Furthermore, a network with significant changes in time was revealed, also showing associations with the level of partner preference. Overall, our findings revealed the association between network-level functional connectivity changes and social bonding.

    1. Developmental Biology
    2. Neuroscience

    Dentate gyrus development requires a cortical hem-derived astrocytic scaffold

    Alessia Caramello et al.
    Research Article Updated

    During embryonic development, radial glial cells give rise to neurons, then to astrocytes following the gliogenic switch. Timely regulation of the switch, operated by several transcription factors, is fundamental for allowing coordinated interactions between neurons and glia. We deleted the gene for one such factor, SOX9, early during mouse brain development and observed a significantly compromised dentate gyrus (DG). We dissected the origin of the defect, targeting embryonic Sox9 deletion to either the DG neuronal progenitor domain or the adjacent cortical hem (CH). We identified in the latter previously uncharacterized ALDH1L1+ astrocytic progenitors, which form a fimbrial-specific glial scaffold necessary for neuronal progenitor migration toward the developing DG. Our results highlight an early crucial role of SOX9 for DG development through regulation of astroglial potential acquisition in the CH. Moreover, we illustrate how formation of a local network, amidst astrocytic and neuronal progenitors originating from adjacent domains, underlays brain morphogenesis.