PXD004334 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Role for KDM3A in ciliogenesis |
Description | Cilia are dynamic antennae that sense the extracellular environment adjusting their length to maintain homeostasis. Mutant mouse models for the lysine demethylase KDM3A (JMJD1A, JMHD2A) share phenotypic features with human ciliopathies, including obesity and metabolic syndrome. Here we show that cilia of Kdm3a mutants are unstable with dysregulated length ranges accumulating intraflagellar transport proteins (IFTs) at the ciliary tip. RNA sequencing and mass-spectrometry identified actin cytoskeleton as the most miss-regulated feature during the ciliary cycle of KDM3A null cells and revealed that IFT81 contains Nε-methylated lysines in vivo to which recombinant KDM3A binds without subsequent demethylation. Mutations in these IFT81 methyl-lysine residues however stabilize KDM3A null cilia and potentiate ciliogenesis surpassing wild type cells; a synergism phenocopied by wild type cultures through the simultaneous destabilization of the actin cytoskeleton when over-expressing IFT81 lysine-mutants. Our work reveals that ciliogenesis requires the coordinated release of cytoskeletal constrains and the presence of intraflagellar transport proteins which KDM3A integrates aided by post-translationally modifiable lysine residues in IFT81. |
HostingRepository | PRIDE |
AnnounceDate | 2018-07-11 |
AnnouncementXML | Submission_2019-02-12_08:08:28.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Alex von kriegsheim |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | No PTMs are included in the dataset |
Instrument | Q Exactive |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2016-06-15 07:04:53 | ID requested | |
1 | 2018-07-11 07:57:28 | announced | |
⏵ 2 | 2019-02-12 08:08:30 | announced | Updated publication reference for PubMed record(s): 28246120. |
Publication List
Yeyati PL, Schiller R, Mali G, Kasioulis I, Kawamura A, Adams IR, Playfoot C, Gilbert N, van Heyningen V, Wills J, von Kriegsheim A, Finch A, Sakai J, Schofield CJ, Jackson IJ, Mill P, KDM3A coordinates actin dynamics with intraflagellar transport to regulate cilia stability. J Cell Biol, 216(4):999-1013(2017) [pubmed] |
Keyword List
curator keyword: Biological |
submitter keyword: Cilia/ Intraflagellar transport/ Histone demethylase/ KDM3A/ lysine methylation/ actin dynamics |
Contact List
alex von kriegsheim |
contact affiliation | university of Edinburgh |
contact email | alex.vonkriegsheim@igmm.ed.ac.uk |
lab head | |
Alex von kriegsheim |
contact affiliation | Systems Biology |
contact email | alex.vonkriegsheim@ucd.ie |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD004334
- Label: PRIDE project
- Name: Role for KDM3A in ciliogenesis