HSP90AA1

Cilia effects upon perturbation of HSP90AA1

Loss-of-function effect:

Cilia resorption

Ciliogenesis screen results (2 screens)

• Wheway et al. 2015 (siRNA) [siRNA]: Ciliogenesis Defect (z=-2.94) PMID:26167766
• Breslow et al. 2018 (CRISPR) [CRISPR]: No Significant Effect PMID:29459680

Phenotypes

Mouse phenotype:

abnormal snout morphology, increased circulating alkaline phosphatase level, increased grip strength, abnormal incisor morphology

Mouse ciliopathy phenotype:

male infertility, abnormal cranium morphology

Subcellular localization

basal body, cytosol, microtubules, nucleus

Functional category

• Ciliary assembly/disassembly
• Trafficking (BBSome, small GTPases, vesicular transport, ATPases)
• Actin & cytoskeleton regulation
• Metabolism
• Reproduction & sperm
• Viral interactions
• Protein processing & maturation
• Signaling (Hedgehog, GPCRs, ion channels)
• Cardiac & muscle development
• Muscle contraction & physiology
• Transcription regulation
• Cilia length regulation

Function

Effector protein in the FOXJ1 regulatory network (30881373). Hsp90伪 shows chaperone activity that might facilitate protein assembly and disassembly during ciliogenesis. Phosphorylated Hsp90伪 is likely to be a component of the distal appendages in the mother centriole (25359884). Hsp90α forms a stable complex at the cilium neck … phosphorylated Hsp90α forms a stable ring around the axoneme … Heat shock treatment causes Hsp90α to dissipate and induces resorption of cilia. (25359884) In unstressed cells, Hsp90 localizes to the ciliary axoneme and its inhibition resulted in cilia loss. (22718348) HSP90 differentially regulates cilia length, subject to oxygen tension. (25171775) In retinal photoreceptors, “No significant change was observed in cilia length between Hsp90α⁻/⁻ and Hsp90α⁺/⁺ animals.” — suggests that in that context, Hsp90α loss did not alter cilia length. (37172722)