The molecular chaperone Hsp90 α deficiency causes retinal degeneration by disrupting Golgi organization and vesicle transportation in photoreceptors.

The molecular chaperone Hsp90α deficiency causes retinal degeneration by disrupting Golgi organization and vesicle transportation in photoreceptors. J Mol Cell Biol. 2019 Aug 13;: Authors: Wu Y, Zheng X, Ding Y, Zhou M, Wei Z, Liu T, Liao K Abstract Heat shock protein 90 (Hsp90) is an abundant molecular chaperone with two isoforms, Hsp90α and β. Hsp90β deficiency causes embryonic lethality, whereas Hsp90α deficiency causes few abnormities except male sterility. In this paper, we reported that Hsp90α was exclusively expressed in retina, testis and brain. Its deficiency caused retinitis pigmentosa (RP), a disease leading to blindness. In Hsp90α-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 Hsp90α-deficient photoreceptors. Proteomic analysis identified microtubule-associated protein 1B (MAP1B) as an Hsp90α-associated protein in photoreceptors. Hsp90α deficiency increased degradation of MAP1B by inducing its ubiquitination, causing α-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 Hsp90α deficiency. Taken together, the microtubule destabilization could be the underlying reason for Hsp90...
Source: Mol Biol Cell - Category: Molecular Biology Authors: Tags: J Mol Cell Biol Source Type: research