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Loss of Tmem30a leads to photoreceptor degeneration

Phosphatidylserine (PS) is asymmetrically distributed between the outer and inner leaflets of the plasma membrane in eukaryotic cells. PS asymmetry on the plasma membrane depends on the activities of P4-ATPases, and disruption of PS distribution can lead to various disease conditions. Folding and tr...

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Autores principales: Zhang, Lin, Yang, Yeming, Li, Shujin, Zhang, Shanshan, Zhu, Xiong, Tai, Zhengfu, Yang, Mu, Liu, Yuqing, Guo, Xinzheng, Chen, Bo, Jiang, Zhilin, Lu, Fang, Zhu, Xianjun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5571223/
https://www.ncbi.nlm.nih.gov/pubmed/28839191
http://dx.doi.org/10.1038/s41598-017-09506-5
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author Zhang, Lin
Yang, Yeming
Li, Shujin
Zhang, Shanshan
Zhu, Xiong
Tai, Zhengfu
Yang, Mu
Liu, Yuqing
Guo, Xinzheng
Chen, Bo
Jiang, Zhilin
Lu, Fang
Zhu, Xianjun
author_facet Zhang, Lin
Yang, Yeming
Li, Shujin
Zhang, Shanshan
Zhu, Xiong
Tai, Zhengfu
Yang, Mu
Liu, Yuqing
Guo, Xinzheng
Chen, Bo
Jiang, Zhilin
Lu, Fang
Zhu, Xianjun
author_sort Zhang, Lin
collection PubMed
description Phosphatidylserine (PS) is asymmetrically distributed between the outer and inner leaflets of the plasma membrane in eukaryotic cells. PS asymmetry on the plasma membrane depends on the activities of P4-ATPases, and disruption of PS distribution can lead to various disease conditions. Folding and transporting of P4-ATPases to their cellular destination requires the β subunit TMEM30A proteins. However, the in vivo functions of Tmem30a remain unknown. To this end, we generated retinal-specific Tmem30a-knockout mice to investigate its roles in vivo for the first time. Our data demonstrated that loss of Tmem30a in mouse cone cells leads to mislocalization of cone opsin, loss of photopic electroretinogram (ERG) responses and loss of cone cells. Mechanistically, Tmem30a-mutant mouse embryonic fibroblasts (MEFs) exhibited diminished PS flippase activity and increased exposure of PS on the cell surface. The broad loss of Tmem30a in adult mice led to a reduced scotopic photoresponse, mislocalization of ATP8A2 to the inner segment and cell body, and increased apoptosis in the retina. Our data demonstrated novel essential roles of Tmem30a in the retina.
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spelling pubmed-55712232017-09-01 Loss of Tmem30a leads to photoreceptor degeneration Zhang, Lin Yang, Yeming Li, Shujin Zhang, Shanshan Zhu, Xiong Tai, Zhengfu Yang, Mu Liu, Yuqing Guo, Xinzheng Chen, Bo Jiang, Zhilin Lu, Fang Zhu, Xianjun Sci Rep Article Phosphatidylserine (PS) is asymmetrically distributed between the outer and inner leaflets of the plasma membrane in eukaryotic cells. PS asymmetry on the plasma membrane depends on the activities of P4-ATPases, and disruption of PS distribution can lead to various disease conditions. Folding and transporting of P4-ATPases to their cellular destination requires the β subunit TMEM30A proteins. However, the in vivo functions of Tmem30a remain unknown. To this end, we generated retinal-specific Tmem30a-knockout mice to investigate its roles in vivo for the first time. Our data demonstrated that loss of Tmem30a in mouse cone cells leads to mislocalization of cone opsin, loss of photopic electroretinogram (ERG) responses and loss of cone cells. Mechanistically, Tmem30a-mutant mouse embryonic fibroblasts (MEFs) exhibited diminished PS flippase activity and increased exposure of PS on the cell surface. The broad loss of Tmem30a in adult mice led to a reduced scotopic photoresponse, mislocalization of ATP8A2 to the inner segment and cell body, and increased apoptosis in the retina. Our data demonstrated novel essential roles of Tmem30a in the retina. Nature Publishing Group UK 2017-08-24 /pmc/articles/PMC5571223/ /pubmed/28839191 http://dx.doi.org/10.1038/s41598-017-09506-5 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Zhang, Lin
Yang, Yeming
Li, Shujin
Zhang, Shanshan
Zhu, Xiong
Tai, Zhengfu
Yang, Mu
Liu, Yuqing
Guo, Xinzheng
Chen, Bo
Jiang, Zhilin
Lu, Fang
Zhu, Xianjun
Loss of Tmem30a leads to photoreceptor degeneration
title Loss of Tmem30a leads to photoreceptor degeneration
title_full Loss of Tmem30a leads to photoreceptor degeneration
title_fullStr Loss of Tmem30a leads to photoreceptor degeneration
title_full_unstemmed Loss of Tmem30a leads to photoreceptor degeneration
title_short Loss of Tmem30a leads to photoreceptor degeneration
title_sort loss of tmem30a leads to photoreceptor degeneration
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5571223/
https://www.ncbi.nlm.nih.gov/pubmed/28839191
http://dx.doi.org/10.1038/s41598-017-09506-5
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