Regulation of the membrane trafficking of the mechanosensitive ion channels trpv1 and trpv4 by zonular tension, osmotic stress and activators in the mouse lens

Yosuke Nakazawa, Rosica S. Petrova, Yuki Sugiyama, Noriaki Nagai, Hiroomi Tamura, Paul J. Donaldson

Research output: Contribution to journalArticlepeer-review

Abstract

Lens water transport generates a hydrostatic pressure gradient that is regulated by a dual-feedback system that utilizes the mechanosensitive transient receptor potential vanilloid (TRPV) channels, TRPV1 and TRPV4, to sense changes in mechanical tension and extracellular osmolarity. Here, we investigate whether the modulation of TRPV1 or TRPV4 activity dynamically affects their membrane trafficking. Mouse lenses were incubated in either pilocarpine or tropicamide to alter zonular tension, exposed to osmotic stress, or the TRPV1 and TRPV4 activators capsaicin andGSK1016790A (GSK101), and the effect on the TRPV1 and TRPV4 membrane trafficking in peripheral fiber cells visualized using confocal microscopy. Decreases in zonular tension caused the removal of TRPV4 from the membrane of peripheral fiber cells. Hypotonic challenge had no effect on TRPV1, but increased the membrane localization of TRPV4. Hypertonic challenge caused the insertion of TRPV1 and the removal of TRPV4 from the membranes of peripheral fiber cells. Capsaicin caused an increase in TRPV4 membrane localization, but had no effect on TRPV1; while GSK101 decreased the membrane localization of TRPV4 and increased the membrane localization of TRPV1. These reciprocal changes in TRPV1/4 membrane localization are consistent with the channels acting as mechanosensitive transducers of a dual‐feedback pathway that regulates lens water transport.

Original languageEnglish
Article number12658
JournalInternational journal of molecular sciences
Volume22
Issue number23
DOIs
Publication statusPublished - 2021 Dec 1

Keywords

  • Cell volume
  • Lens
  • Mechanosensors
  • Osmotic stress
  • TRPV1/4
  • Zonular tension

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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