| First Author | Wu Y | Year | 2019 |
| Journal | J Mol Cell Biol | PubMed ID | 31408169 |
| Mgi Jnum | J:283232 | Mgi Id | MGI:6386677 |
| Doi | 10.1093/jmcb/mjz048 | Citation | Wu Y, et al. (2019) The molecular chaperone Hsp90alpha deficiency causes retinal degeneration by disrupting Golgi organization and vesicle transportation in photoreceptors. J Mol Cell Biol |
| abstractText | Heat shock protein 90 (Hsp90) is an abundant molecular chaperone with two isoforms, Hsp90alpha and beta. Hsp90beta deficiency causes embryonic lethality, whereas Hsp90alpha deficiency causes few abnormities except male sterility. In this paper, we reported that Hsp90alpha was exclusively expressed in retina, testis and brain. Its deficiency caused retinitis pigmentosa (RP), a disease leading to blindness. In Hsp90alpha-deficient mice, retina was deteriorated and the outer segment of photoreceptor was deformed. Immunofluorescence staining and electron microscopic analysis revealed disintegrated Golgi and aberrant intersegmental vesicle transportation in Hsp90alpha-deficient photoreceptors. Proteomic analysis identified microtubule-associated protein 1B (MAP1B) as an Hsp90alpha-associated protein in photoreceptors. Hsp90alpha deficiency increased degradation of MAP1B by inducing its ubiquitination, causing alpha-tubulin deacetylation and microtubule destabilization. Furthermore, the treatment of wild-type mice with 17-DMAG, an Hsp90 inhibitor of geldanamycin derivative, induced the same retinal degeneration as Hsp90alpha deficiency. Taken together, the microtubule destabilization could be the underlying reason for Hsp90alpha deficiency induced retinitis pigmentosa. |
