| First Author | Ghosh S | Year | 2021 |
| Journal | Commun Biol | Volume | 4 |
| Issue | 1 | Pages | 248 |
| PubMed ID | 33627831 | Mgi Jnum | J:306517 |
| Mgi Id | MGI:6715004 | Doi | 10.1038/s42003-021-01763-5 |
| Citation | Ghosh S, et al. (2021) betaA1-crystallin regulates glucose metabolism and mitochondrial function in mouse retinal astrocytes by modulating PTP1B activity. Commun Biol 4(1):248 |
| abstractText | betaA3/A1-crystallin, a lens protein that is also expressed in astrocytes, is produced as betaA3 and betaA1-crystallin isoforms by leaky ribosomal scanning. In a previous human proteome high-throughput array, we found that betaA3/A1-crystallin interacts with protein tyrosine phosphatase 1B (PTP1B), a key regulator of glucose metabolism. This prompted us to explore possible roles of betaA3/A1-crystallin in metabolism of retinal astrocytes. We found that betaA1-crystallin acts as an uncompetitive inhibitor of PTP1B, but betaA3-crystallin does not. Loss of betaA1-crystallin in astrocytes triggers metabolic abnormalities and inflammation. In CRISPR/cas9 gene-edited betaA1-knockdown (KD) mice, but not in betaA3-knockout (KO) mice, the streptozotocin (STZ)-induced diabetic retinopathy (DR)-like phenotype is exacerbated. Here, we have identified betaA1-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 betaA1-crystallin and higher levels of PTP1B in the vitreous humor. |
