Eph-ephrin Signaling Affects Eye Lens Fiber Cell Intracellular Voltage and Membrane Conductance

The avascular eye lens generates its own microcirculation that is required for maintaining lifelong lens transparency. The microcirculation relies on sodium ion flux, an extensive network of gap junction (GJ) plaques between lens fiber cells and transmembrane water channels. Disruption of connexin p...

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Autores principales:	Catherine Cheng, Junyuan Gao, Xiurong Sun, Richard T. Mathias
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	gap junction coupling resistivity connexin aquaporin EphA2 ephrin-A5 Physiology QP1-981
Acceso en línea:	https://doaj.org/article/7469d467587141e2b39620984c2e9a19
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spelling	oai:doaj.org-article:7469d467587141e2b39620984c2e9a192021-12-01T02:37:46ZEph-ephrin Signaling Affects Eye Lens Fiber Cell Intracellular Voltage and Membrane Conductance1664-042X10.3389/fphys.2021.772276https://doaj.org/article/7469d467587141e2b39620984c2e9a192021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fphys.2021.772276/fullhttps://doaj.org/toc/1664-042XThe avascular eye lens generates its own microcirculation that is required for maintaining lifelong lens transparency. The microcirculation relies on sodium ion flux, an extensive network of gap junction (GJ) plaques between lens fiber cells and transmembrane water channels. Disruption of connexin proteins, the building blocks of GJs, or aquaporins, which make up water and adhesion channels, lead to lens opacification or cataracts. Recent studies have revealed that disruption of Eph-ephrin signaling, in particular the receptor EphA2 and the ligand ephrin-A5, in humans and mice lead to congenital and age-related cataracts. We investigated whether changes in lens transparency in EphA2 or ephrin-A5 knockout (–/–) mice is related to changes in GJ coupling and lens fluid and ion homeostasis. Immunostaining revealed changes in connexin 50 (Cx50) subcellular localization in EphA2–/– peripheral lens fibers and alteration in aquaporin 0 (Aqp0) staining patterns in ephrin-A5–/– and EphA2–/– inner mature fiber cells. Surprisingly, there was no obvious change in GJ coupling in knockout lenses. However, there were changes in fiber cell membrane conductance and intracellular voltage in knockout lenses from 3-month-old mice. These knockout lenses displayed decreased conductance of mature fiber membranes and were hyperpolarized compared to control lenses. This is the first demonstration that the membrane conductance of lens fibers can be regulated. Together these data suggest that EphA2 may be needed for normal Cx50 localization to the cell membrane and that conductance of lens fiber cells requires normal Eph-ephrin signaling and water channel localization.Catherine ChengJunyuan GaoXiurong SunRichard T. MathiasFrontiers Media S.A.articlegap junction couplingresistivityconnexinaquaporinEphA2ephrin-A5PhysiologyQP1-981ENFrontiers in Physiology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	gap junction coupling resistivity connexin aquaporin EphA2 ephrin-A5 Physiology QP1-981
spellingShingle	gap junction coupling resistivity connexin aquaporin EphA2 ephrin-A5 Physiology QP1-981 Catherine Cheng Junyuan Gao Xiurong Sun Richard T. Mathias Eph-ephrin Signaling Affects Eye Lens Fiber Cell Intracellular Voltage and Membrane Conductance
description	The avascular eye lens generates its own microcirculation that is required for maintaining lifelong lens transparency. The microcirculation relies on sodium ion flux, an extensive network of gap junction (GJ) plaques between lens fiber cells and transmembrane water channels. Disruption of connexin proteins, the building blocks of GJs, or aquaporins, which make up water and adhesion channels, lead to lens opacification or cataracts. Recent studies have revealed that disruption of Eph-ephrin signaling, in particular the receptor EphA2 and the ligand ephrin-A5, in humans and mice lead to congenital and age-related cataracts. We investigated whether changes in lens transparency in EphA2 or ephrin-A5 knockout (–/–) mice is related to changes in GJ coupling and lens fluid and ion homeostasis. Immunostaining revealed changes in connexin 50 (Cx50) subcellular localization in EphA2–/– peripheral lens fibers and alteration in aquaporin 0 (Aqp0) staining patterns in ephrin-A5–/– and EphA2–/– inner mature fiber cells. Surprisingly, there was no obvious change in GJ coupling in knockout lenses. However, there were changes in fiber cell membrane conductance and intracellular voltage in knockout lenses from 3-month-old mice. These knockout lenses displayed decreased conductance of mature fiber membranes and were hyperpolarized compared to control lenses. This is the first demonstration that the membrane conductance of lens fibers can be regulated. Together these data suggest that EphA2 may be needed for normal Cx50 localization to the cell membrane and that conductance of lens fiber cells requires normal Eph-ephrin signaling and water channel localization.
format	article
author	Catherine Cheng Junyuan Gao Xiurong Sun Richard T. Mathias
author_facet	Catherine Cheng Junyuan Gao Xiurong Sun Richard T. Mathias
author_sort	Catherine Cheng
title	Eph-ephrin Signaling Affects Eye Lens Fiber Cell Intracellular Voltage and Membrane Conductance
title_short	Eph-ephrin Signaling Affects Eye Lens Fiber Cell Intracellular Voltage and Membrane Conductance
title_full	Eph-ephrin Signaling Affects Eye Lens Fiber Cell Intracellular Voltage and Membrane Conductance
title_fullStr	Eph-ephrin Signaling Affects Eye Lens Fiber Cell Intracellular Voltage and Membrane Conductance
title_full_unstemmed	Eph-ephrin Signaling Affects Eye Lens Fiber Cell Intracellular Voltage and Membrane Conductance
title_sort	eph-ephrin signaling affects eye lens fiber cell intracellular voltage and membrane conductance
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/7469d467587141e2b39620984c2e9a19
work_keys_str_mv	AT catherinecheng ephephrinsignalingaffectseyelensfibercellintracellularvoltageandmembraneconductance AT junyuangao ephephrinsignalingaffectseyelensfibercellintracellularvoltageandmembraneconductance AT xiurongsun ephephrinsignalingaffectseyelensfibercellintracellularvoltageandmembraneconductance AT richardtmathias ephephrinsignalingaffectseyelensfibercellintracellularvoltageandmembraneconductance
_version_	1718405910040150016

Eph-ephrin Signaling Affects Eye Lens Fiber Cell Intracellular Voltage and Membrane Conductance

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