Regulation of the Membrane Trafficking of the Mechanosensitive Ion Channels TRPV1 and TRPV4 by Zonular Tension, Osmotic Stress and Activators in the Mouse Lens

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.

Piezo2 expression and its alteration by mechanical forces in mouse mesangial cells and renin-producing cells

“…For example, Du et al 44 reported that Trpv4, Piezo1, and Piezo2 are expressed on the same chondrocyte, each of which transduces mechanical stimuli differentially, depending on the stimulus intensities. Nakazawa et al 45 reported that Trpv1 and Trpv4 are expressed in lens surface cells. Trpv1 senses decreased pressure or hyperosmotic stress, whereas Trpv4 senses increased pressure or hypoosmotic stress.…”

Proteome Remodeling of the Eye Lens at 50 Years Identified with Data-Independent Acquisition

“…It should be emphasized that a protein not detected in this study is not indicative of protein absence from the lens. For example, while putatively involved in osmotic regulation of the lens and regulation of MCS current (18, 55, 56), neither TRPV1/4 were measured in any cortex sample. Immunohistochemistry in murine and porcine lenses supports the cortical presence of these proteins (55, 57, 58); however, no mass spectrometry reports support the presence of TRPV1/4 in the human lens cortex.…”

“…The resulting potential, coupled to aquaporin water transport and gap junction intercellular contacts leads to a net current of metabolite convection into the lens at the anterior and posterior poles (15,16)(Figure 1B). Although unshown in Figure 1, it is also hypothesized that transient receptor potential cation channel subfamily V members 1 and 4 (TRPV1/4) mediate fiber cell osmolarity by regulation of Na/K ATPase activity and Aquaporin-5 trafficking to the plasma membrane (12,(17)(18)(19).…”

Lens Aquaporins in Health and Disease: Location is Everything!

“…This scheme is based on earlier model ( Gao et al, 2015 ; Shahidullah et al, 2018 ). The figure and figure caption are reused with no special permission under an open access Creative Common CC BY license published by MDPI from ( Nakazawa et al, 2021 ).…”