Hsp90α forms a stable complex at cilia neck for signal molecules interaction in cilia-mediated IGF-1 receptor signaling

Abstract

The primary cilium is composed of an axoneme that protrudes from the cell surface, a basal body beneath the membrane and a transition neck in between. It is a sensory organelle on the plasma membrane, involved in mediating extracellular signals. In the transition neck region of the cilium, the microtubules change from triplet to doublet microtubules. This region also contains the transition fibres that crosslink the axoneme with the membrane and the necklace proteins that regulate molecules being transported into and out of the cilium. In this protein-enriched, complex area it is important to maintain the correct assembly of all of these proteins. Here, through immunofluorescent staining and protein isolation, we identify the molecular chaperone Hsp90a clustered at the periciliary base. At the transition neck region, phosphorylated Hsp90a forms a stable ring around the axoneme. Heat shock treatment causes Hsp90a to dissipate and induces resorption of cilia. We further identify that Hsp90a at the transition neck region represents a signalling platform on which IRS-1 interacts with intracellular downstream signalling molecules involved in IGF-1 receptor signalling.

HSP90 inhibitor geldanamycin reverts IL-13– and IL-17–induced airway goblet cell metaplasia

“…In contrast, mouse club cells transdifferentiate into goblet cells in vivo (15,(135)(136)(137)(138). Interestingly, heat shock-induced dissociation of HSP90 from cilia leads to cilia resorption (95). Previous reports suggest but do not demonstrate that goblet cells might transdifferentiate into ciliated or other cell types (10,139).…”

Structural and Functional Recovery of Sensory Cilia in C. elegans IFT Mutants upon Aging

“…In Tetrahymena and Chlamydomonas , flagellar defects due to partial loss of IFT proteins can be bypassed in some suppressor strains under conditions of oxygen deprivation [80, 91–93], and it has been suggested that a stress-induced chaperone mechanism stabilizes the IFT-B complex to permit cilia function under these conditions [92]. Moreover, Hsp90 is localized to cilia, and regulates cilia stability in response to stress in mammalian cells [94–96]. Our observations indicate that while IFT protein function is essential for ciliogenesis, compromised IFT complex function can be partly bypassed during early stages of adult aging or under other conditions of stress to promote cilia lengthening.…”

Structural and Functional Recovery of Sensory Cilia in C. elegans IFT Mutants upon Aging

“…In Tetrahymena and Chlamydomonas, flagellar defects due to partial loss of IFT proteins can be bypassed in some suppressor strains under conditions of oxygen deprivation [80,[91][92][93], and it has been suggested that a stress-induced chaperone mechanism stabilizes the IFT-B complex to permit cilia function under these conditions [92]. Moreover, Hsp90 is localized to cilia, and regulates cilia stability in response to stress in mammalian cells [94][95][96]. Our observations indicate that while IFT protein function is essential for ciliogenesis, compromised IFT complex function can be partly bypassed during early stages of adult aging or under other conditions of stress to promote cilia lengthening.…”