NHE8 is essential for RPE cell polarity and photoreceptor survival

Scientific Reports
Chun-hong XiaXiaohua Gong

Abstract

A new N-ethyl-N-nitrosourea (ENU)-induced mouse recessive mutation, identified by fundus examination of the eye, develops depigmented patches, indicating retinal disorder. Histology data show aberrant retinal pigment epithelium (RPE) and late-onset photoreceptor cell loss in the mutant retina. Chromosomal mapping and DNA sequencing reveal a point mutation (T to A) of the Slc9a8 gene, resulting in mutant sodium/proton exchanger 8 (NHE8)-M120K protein. The lysine substitution decreases the probability of forming the 3(rd) transmembrane helix, which impairs the pore structure of the Na(+)/H(+) exchanger. Various RPE defects, including mislocalization of the apical marker ezrin, and disrupted apical microvilli and basal infoldings are observed in mutant mice. We have further generated NHE8 knockout mice and confirmed similar phenotypes, including abnormal RPE cells and late-onset photoreceptor cell loss. Both in vivo and in vitro data indicate that NHE8 co-localizes with ER, Golgi and intracellular vesicles in RPE cells. Thus, NHE8 function is necessary for the survival of photoreceptor cells and NHE8 is important for RPE cell polarity and function. Dysfunctional RPE may ultimately lead to photoreceptor cell death in the NHE8 mutan...Continue Reading

References

Apr 1, 1967·The Journal of Cell Biology·R W Young
Jan 1, 1993·Journal of Cell Science. Supplement·D Bok
Dec 30, 1999·The Journal of Cell Biology·V L BonilhaE Rodriguez-Boulan
Mar 4, 2000·Human Molecular Genetics·P M D'CruzD Vollrath
Dec 12, 2001·Traffic·A D Marmorstein
Feb 1, 2003·Traffic·Ora A Weisz
Feb 26, 2003·Investigative Ophthalmology & Visual Science·Nancy J PhilpPaul J Linser
Jul 8, 2003·Pflügers Archiv : European journal of physiology·John Orlowski, Sergio Grinstein
Dec 15, 2004·The Journal of Experimental Medicine·Emeline F NandrotSilvia C Finnemann
Jan 12, 2005·American Journal of Physiology. Cell Physiology·Christopher L BrettRajini Rao
Jul 1, 2005·Physiological Reviews·Olaf Strauss
Nov 2, 2005·Proceedings of the National Academy of Sciences of the United States of America·Ami A DeoraEnrique Rodriguez-Boulan
Nov 18, 2005·Experimental Eye Research·Vera L BonilhaJoe G Hollyfield
Jan 26, 2007·Advances in Experimental Medicine and Biology·Chun-hong XiaXiaohua Gong
Jul 25, 2007·Current Opinion in Cell Biology·John Orlowski, Sergio Grinstein
Nov 10, 2007·Science·Jonathan H LinPeter Walter
Feb 12, 2008·Human Molecular Genetics·Chun-Hong XiaXiaohua Gong
Mar 21, 2008·Nature Reviews. Molecular Cell Biology·Maria Antonietta De Matteis, Alberto Luini
Jun 6, 2008·American Journal of Physiology. Cell Physiology·Lauren L DanieleNancy J Philp
Mar 20, 2010·Advances in Experimental Medicine and Biology·Emeline F Nandrot, Eric M Dufour
Aug 20, 2010·Molecular Biology of the Cell·Scott P LawrenceKatherine Bowers
Apr 3, 2012·Genes & Development·Toshihiko ToyofukuAtsushi Kumanogoh
Jul 17, 2012·Neuron·Jayakrishna Ambati, Benjamin J Fowler
Nov 15, 2012·Methods in Molecular Biology·John G Flannery, Meike Visel
May 10, 2013·American Journal of Physiology. Cell Physiology·Chang LiuFayez K Ghishan
Nov 12, 2013·Progress in Retinal and Eye Research·Yogesan KanagasingamTien Y Wong
Mar 5, 2014·Proceedings of the National Academy of Sciences of the United States of America·Roland ThuenauerChing-Hwa Sung
Mar 22, 2014·Nature Reviews. Molecular Cell Biology·Enrique Rodriguez-Boulan, Ian G Macara
Apr 1, 2014·Current Opinion in Cell Biology·Tivadar OrbanKrzysztof Palczewski
May 2, 2014·Experimental Eye Research·Francesca MazzoniSilvia C Finnemann
Aug 26, 2014·Experimental Eye Research·Guillermo L LehmannEnrique Rodriguez-Boulan
Aug 26, 2014·Experimental Eye Research·Nadine Reichhart, Olaf Strauss

❮ Previous
Next ❯

Citations

May 10, 2017·The Journal of Biological Chemistry·Karina OberheideThomas J Jentsch
Feb 28, 2020·Progress in Retinal and Eye Research·Aparna LakkarajuDavid S Williams

❮ Previous
Next ❯

Methods Mentioned

BETA
Knockout
PCR

Software Mentioned

ImageJ
Ensembl
TMHMM
Ensembl Mouse Genome Server

Related Concepts

Related Feeds

Cell Atlas of the Human Eye

Constructing a cell atlas of the human eye will require transcriptomic and histologic analysis over the lifespan. This understanding will aid in the study of development and disease. Find the latest research pertaining to the Cell Atlas of the Human Eye here.

Related Papers

Investigative Ophthalmology & Visual Science
Vera L Bonilha, E Rodriguez-Boulan
Advances in Experimental Medicine and Biology
Vera L BonilhaJoe G Hollyfield
Experimental Eye Research
Vera L BonilhaJoe G Hollyfield
Investigative Ophthalmology & Visual Science
Chun-Hong XiaXiaohua Gong
© 2021 Meta ULC. All rights reserved