NHE8 is essential for RPE cell polarity and photoreceptor survival.
NHE8 is essential for RPE cell polarity and photoreceptor survival.
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DOI：
10.1038/srep09358
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发表时间：
2015-03-20
影响因子：
4.6
通讯作者：
Gong X
中科院分区：
文献类型：
--
作者：
Xia CH;Liu H;Cheung D;Tang F;Chang B;Li M;Gong X
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 3rd 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 mutants. Further studies will be needed to elucidate whether or not NHE8 regulates pH homeostasis in the protein secretory pathways of RPE.
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DOI：
10.1084/jem.20041447
发表时间：
2004-12-20
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Nandrot EF;Kim Y;Brodie SE;Huang X;Sheppard D;Finnemann SC
通讯作者：
Finnemann SC
影响因子：
3.4
作者：
Mazzoni, Francesca;Safa, Hussein;Finnemann, Silvia C.
通讯作者：
Finnemann, Silvia C.
影响因子：
3.7
作者：
Hayashi H;Tamura A;Krishnan D;Tsukita S;Suzuki Y;Kocinsky HS;Aronson PS;Orlowski J;Grinstein S;Alexander RT
通讯作者：
Alexander RT
影响因子：
5.5
作者：
Daniele, Lauren L.;Sauer, Brian;Philp, Nancy J.
通讯作者：
Philp, Nancy J.
影响因子：
30.8
作者：
Gal, A;Li, Y;Vollrath, D
通讯作者：
Vollrath, D