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

Abstract

Morgana (Mora, also known as CHORD in flies) and its mammalian homologue, called CHORDC1 or CHP1, is a highly conserved cysteine and histidine-rich domain (CHORD)-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 mora causes lethality and a complex mitotic phenotype that is rescued by a human morgana transgene. Here, we show that Drosophila Mora localises to mitotic spindles and co-purifies with the Hsp90-R2TP-TTT supercomplex and with additional well-known Hsp90 co-chaperones. Acute inhibition of Mora 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 to microtubules directly and promotes microtubule polymerisation in vitro, suggesting that Mora directly regulates spindle dynamics independently of its Hsp90 co-chaperone role.

Oncolytic Virus Affects the RAS Pathway in Cancer: RNA Sequence Analysis

“…CHORDC1, as other HSP90 co-chaperones, suppresses the aggregation of denatured proteins. HSP90 and its co-chaperones mediate protein conformation shifts during the cell cycle [17]. It has been shown that reduction of CHORDC1 leads to defective chromosome condensation and spindle formation, as well as tumorigenesis, as a result of altered HSP90 activity [17].…”

“…HSP90 and its co-chaperones mediate protein conformation shifts during the cell cycle [17]. It has been shown that reduction of CHORDC1 leads to defective chromosome condensation and spindle formation, as well as tumorigenesis, as a result of altered HSP90 activity [17]. RTN4 belongs to the family of reticulon encoding genes which are associated with the endoplasmic reticulum.…”

Extracellular HSP90 Machineries Build Tumor Microenvironment and Boost Cancer Progression

“…Inside the cells, Morgana regulates signal transduction by binding and inhibiting Rho kinases I and II ( Ferretti et al, 2010 ; Fusella et al, 2014 ) and promotes NF-kB activation ( Fusella et al, 2017 ). It is also involved in microtubule polymerization ( Palumbo et al, 2020 ), EGF receptor trafficking ( Haag et al, 2020 ), and extracellular vesicle secretion ( Urabe et al, 2020 ). We recently found that Morgana is secreted by several cancer cells through an unconventional pathway and it associates with HSP90 in the extracellular milieu.…”

miR-15a targets the HSP90 co-chaperone Morgana in chronic myeloid leukemia

“…Morgana is a ubiquitous chaperone protein, essential for Drosophila and mouse development [1][2][3] . Morgana binds to the Heat Shock Protein 90 (HSP90) 1,2,[4][5][6][7][8] , acting as its co-chaperone 8 , and to Rho kinase I and II (ROCKI and ROCKII), inhibiting their activity 3,[9][10][11] .…”

“…Morgana is a ubiquitous chaperone protein, essential for Drosophila and mouse development [1][2][3] . Morgana binds to the Heat Shock Protein 90 (HSP90) 1,2,[4][5][6][7][8] , acting as its co-chaperone 8 , and to Rho kinase I and II (ROCKI and ROCKII), inhibiting their activity 3,[9][10][11] . Our laboratory also demonstrated that Morgana is a component of the IKK complex, essential to sustain NF-κB activation 12,13 .…”