Drosophila Morgana is an Hsp90-interacting protein with a direct role in microtubule polymerization

Abstract

Morgana/CHORDC1/CHP1 is a highly conserved CHORD (Cysteine and Histidine Rich Domain) containing protein that has been proposed to function as an Hsp90 co-chaperone. Morgana deregulation promotes carcinogenesis in both mice and humans while, in Drosophila, loss of morgana (mora) causes lethality and a complex mitotic phenotype that is rescued by a human morgana transgene. Here, we show that Drosophila Morgana localizes to mitotic spindles and co-purifies with the Hsp90-R2TP-TTT super-complex, and with additional well-known Hsp90 co-chaperones. Acute inhibition of Morgana function in the early embryo results in a dramatic reduction in centrosomal microtubule stability, leading to small spindles nucleated from mitotic chromatin. Purified Mora binds microtubules directly and promotes microtubule polymerization in vitro, suggesting that Mora directly regulates spindle dynamics independently of its Hsp90 co-chaperone role.