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

doi:10.1038/s41598-017-09506-5

Cited by 28Retinal Development and DisordersCellular transport and secretionLipid Membrane Structure and Behavior

The DOI matches its Crossref record; 39 of the 39 references it cites were found in a registry or an index.

Loss of Tmem30a leads to photoreceptor degeneration

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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·2017·Scientific Reports

DOI 10.1038/s41598-017-09506-5PMC PMC5571223

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Abstract

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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The Atg5ΔRPE mouse exhibits elevated levels of oxidatively modified lipids, proteins, and DNA with occasional RPE hypertrophy.
“The Atg5ΔRPE mouse also exhibits elevated levels of oxidatively-modified lipids, proteins, and DNA with occasional RPE hypertrophy (Zhang et al., 2017).”
From The cell biology of the retinal pigment epithelium (2020) · cites this paper as Zhang et al., 2017
Retinal degeneration was observed in 35-45% of mice between 8 and 24 months of age.
“Retinal degeneration was observed in 35–45% of mice between 8 and 24 months of age.”
From The cell biology of the retinal pigment epithelium (2020) · cites this paper as Zhang et al., 2017
RPE-specific deletions of Atg5 or Atg7 cause multiple RPE abnormalities including pigmentation defects, vacuolization, accumulation of undigested cellular debris, and atrophy in aged mice.
“RPE-specific deletions of Atg5 or Atg7 cause multiple RPE abnormalities including pigmentation defects, vacuolization, accumulation of undigested cellular debris, and atrophy in aged mice (Zhang et al., 2017).”
From The cell biology of the retinal pigment epithelium (2020) · cites this paper as Zhang et al., 2017

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The cell biology of the retinal pigment epithelium
Lakkaraju, A., Umapathy, A., Tan, L. X., Daniele, L., Philp, N. J., Boesze-Battaglia, K., & Williams, D. S. (2020) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2020.100846 · Cited by 422
“Energetics of the outer retina II: Calculation of a spatio-temporal energy budget in retinal pigment epithelium and photoreceptor cells based on quantification of cellular processes”
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Authors: Zhang, L., Yang, Y., Li, S., Zhang, S., Zhu, X., Tai, Z., Yang, M., Liu, Y., Guo, X., Chen, B., Jiang, Z., Lu, F., & Zhu, X.
Affiliations: University of Electronic Science and Technology of China (CN)
Yale University (US)
Corresponding author: Lu, Fang
Zhu, Xianjun
ORCID: Zhang, Lin
Yang, Yeming
Li, Shujin
Zhang, Shanshan
Tai, Zhengfu
Yang, Mu
Liu, Yuqing
Guo, Xinzheng
Chen, Bo
Jiang, Zhilin
Zhu, Xianjun
Venue: Scientific Reports
Publisher: Springer Science and Business Media LLC
Published: 2017-08-24
Volume: 7
Issue: 1
Pages: 9296-9296
ISSN: 2045-2322 (ISSN-L)
DOI: 10.1038/s41598-017-09506-5
PMC: PMC5571223
OpenAlex: W2749652970
Cited by: 28
References: 39
Citations by year: 2026: 1 · 2025: 3 · 2024: 3 · 2023: 5 · 2021: 5 · 2020: 5 · 2019: 1 · 2018: 4 · 2017: 1
FWCI: 1.23
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0 (tdm)
creativecommons.org/licenses/by/4.0 (vor)
Locations: Scientific Reports (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
Funders: National Natural Science Foundation of China (81271007, 2016TD0009, 2016M600734, 81470668, 2017TJPT0010)
China Postdoctoral Science Foundation (81470668, 2016M600734)
Department of Science and Technology of Sichuan Province (2014JQ0023, 81470668, 2016TD0009, 2017TJPT0010)
Topics: Health Sciences › Medicine › Ophthalmology › Retinal Development and Disorders
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Lipid Membrane Structure and Behavior
Keywords: TMEM30A, photoreceptor degeneration, P4-ATPase, ATP8A2, retinal apoptosis, electroretinogram
MeSH terms: Adenosine Triphosphatases, Animals, Cells, Cultured, Electroretinography, Membrane Proteins, Phosphatidylserines, Retina, Apoptosis, Retinal Cone Photoreceptor Cells, Mice, Knockout, Protein Transport, Phospholipid Transfer Proteins, Color Vision, Night Vision, Opsins

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Loss of Tmem30a leads to photoreceptor degeneration

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