Dataset Information

DNAAF9 interactome from human airway epithelial cells

ABSTRACT: Biogenesis of motile cilia in multiciliated cells (MCCs) is coupled to large-scale biosynthesis of force generating dynein motors. Shulin inhibits pre-assembled ODA (outer dynein arm) motors by packaging them into a closed conformation preventing aberrant off-target interactions with cellular microtubules in multiciliated Tetrahymena cells and co-localises with them in growing cilia. How packaged ODAs engage the Intraflagellar Transport machinery (IFT) to transit from the cytoplasm into growing cilia remains unclear. The mechanism of Shulin’s release for ODA activation inside cilia is also poorly resolved. Using proteomics, we establish links between DNAAF9 (human Shulin) and mammalian ODAs, the anterograde IFT-B complex and a ciliary small GTPase called ARL3. Based on our findings, we propose that Shulin/DNAAF9 enforces ODA inhibition to aid their unimpeded trafficking from the cytoplasm into growing multicilia via IFT and once inside the ciliary compartment, ARL3-GTP competes for a binding site to destabilise the ODA-Shulin complex thereby promoting ODA motor activation.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Lung, Epithelial Cell

SUBMITTER: Girish Mali

LAB HEAD: Girish Ram Mali

PROVIDER: PXD052722 | Pride | 2025-07-31

REPOSITORIES: Pride

ACCESS DATA

Dataset's files

Source:

Items per page:

1 - 5 of 7

Similar Datasets

Project description:Study Smoking and COPD are associated with decreased mucociliary clearance and healthy smokers have shorter cilia in the large airway than nonsmokers. Intraflagellar transport (IFT) is the process by which cilia are produced and maintained. We assessed expression of IFT-related genes in smokers and nonsmokers and evaluated cilia length in the large and small airway of nonsmokers, healthy smokers, and smokers with COPD. Methods Airway epithelium was obtained via bronchoscopic brushing. Affymetrix microarrays were used to evaluate IFT gene expression in 2 independent data sets from large and small airway. Cilia length was assessed by measuring 100 cilia (10 cilia on each of 10 cells) per subject. Results All 40 IFT genes were expressed in the human large and small airway epithelium. In the large airway, 10 IFT genes were down-regulated and 1 up-regulated in smokers. In the small airway, 11 genes were down-regulated and 3 up-regulated in smokers. A set of 8 IFT genes was down-regulated in both data sets. In the large and small airway epithelium, cilia were significantly shorter in healthy smokers than nonsmokers, and significantly shorter in COPD smokers than in both healthy smokers and nonsmokers. Answer to the Question These results support the concept that loss of cilia length contributes to defective mucociliary clearance in COPD, and that smoking-induced changes in expression of IFT genes may be one mechanism of abnormally short cilia in smokers. Strategies to normalize cilia length may be an important avenue for novel COPD therapies. Gene expression was assessed for 40 intraflagellar transport related genes in the LAE of nonsmokers (n=21) and healthy smokers (n=31) and the SAE of an independent group of nonsmokers (n=28) and healthy smokers (n=69). Cilia length was assessed in a total of 228 airway epithelium samples, including 120 LAE samples and 108 SAE samples; a subset of the 228 samples is represented among the 149 samples in this Series.

			Action	DRS
	300323_12PlexTMT_PS.msf	Msf
	300323_Fraction_1.raw	Raw
	300323_Fraction_2.raw	Raw
	300323_Fraction_3.raw	Raw
	300323_Fraction_4.raw	Raw

Dataset Information

DNAAF9 interactome from human airway epithelial cells

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets