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

ABSTRACT: Heat shock protein 90 (Hsp90) is an abundant molecular chaperone with two isoforms, Hsp90? and Hsp90?. Hsp90? deficiency causes embryonic lethality, whereas Hsp90? deficiency causes few abnormities except male sterility. In this paper, we reported that Hsp90? was exclusively expressed in the retina, testis, and brain. Its deficiency caused retinitis pigmentosa (RP), a disease leading to blindness. In Hsp90?-deficient mice, the 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 Hsp90?-deficient photoreceptors. Proteomic analysis identified microtubule-associated protein 1B (MAP1B) as an Hsp90?-associated protein in photoreceptors. Hsp? deficiency increased degradation of MAP1B by inducing its ubiquitination, causing ?-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 Hsp90? deficiency. Taken together, the microtubule destabilization could be the underlying reason for Hsp90? deficiency-induced RP.

SUBMITTER: Wu Y 

PROVIDER: S-EPMC7181719 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature