Dataset Information

?A1-crystallin regulates glucose metabolism and mitochondrial function in mouse retinal astrocytes by modulating PTP1B activity.

ABSTRACT: ?A3/A1-crystallin, a lens protein that is also expressed in astrocytes, is produced as ?A3 and ?A1-crystallin isoforms by leaky ribosomal scanning. In a previous human proteome high-throughput array, we found that ?A3/A1-crystallin interacts with protein tyrosine phosphatase 1B (PTP1B), a key regulator of glucose metabolism. This prompted us to explore possible roles of ?A3/A1-crystallin in metabolism of retinal astrocytes. We found that ?A1-crystallin acts as an uncompetitive inhibitor of PTP1B, but ?A3-crystallin does not. Loss of ?A1-crystallin in astrocytes triggers metabolic abnormalities and inflammation. In CRISPR/cas9 gene-edited ?A1-knockdown (KD) mice, but not in ?A3-knockout (KO) mice, the streptozotocin (STZ)-induced diabetic retinopathy (DR)-like phenotype is exacerbated. Here, we have identified ?A1-crystallin as a regulator of PTP1B; loss of this regulation may be a new mechanism by which astrocytes contribute to DR. Interestingly, proliferative diabetic retinopathy (PDR) patients showed reduced ?A1-crystallin and higher levels of PTP1B in the vitreous humor.

SUBMITTER: Ghosh S

PROVIDER: S-EPMC7904954 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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βA1-crystallin regulates glucose metabolism and mitochondrial function in mouse retinal astrocytes by modulating PTP1B activity.

Ghosh Sayan S Liu Haitao H Yazdankhah Meysam M Stepicheva Nadezda N Shang Peng P Vaidya Tanuja T Hose Stacey S Gupta Urvi U Calderon Michael Joseph MJ Hu Ming-Wen MW Nair Archana Padmanabhan AP Weiss Joseph J Fitting Christopher S CS Bhutto Imran A IA Gadde Santosh Gopi Krishna SGK Naik Naveen Kumar NK Jaydev Chaitra C Lutty Gerard A GA Handa James T JT Jayagopal Ashwath A Qian Jiang J Sahel José-Alain JA Rajasundaram Dhivyaa D Sergeev Yuri Y Zigler J Samuel JS Sethu Swaminathan S Watkins Simon S Ghosh Arkasubhra A Sinha Debasish D

Communications biology 20210224 1

βA3/A1-crystallin, a lens protein that is also expressed in astrocytes, is produced as βA3 and βA1-crystallin isoforms by leaky ribosomal scanning. In a previous human proteome high-throughput array, we found that βA3/A1-crystallin interacts with protein tyrosine phosphatase 1B (PTP1B), a key regulator of glucose metabolism. This prompted us to explore possible roles of βA3/A1-crystallin in metabolism of retinal astrocytes. We found that βA1-crystallin acts as an uncompetitive inhibitor of PTP1B ...[more]

PMID: 33627831

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Dataset Information

?A1-crystallin regulates glucose metabolism and mitochondrial function in mouse retinal astrocytes by modulating PTP1B activity.

Publications

βA1-crystallin regulates glucose metabolism and mitochondrial function in mouse retinal astrocytes by modulating PTP1B activity.

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