PXD004334

PXD004334 is an original dataset announced via ProteomeXchange.

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

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.

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]

curator keyword: Biological

submitter keyword: Cilia/ Intraflagellar transport/ Histone demethylase/ KDM3A/ lysine methylation/ actin dynamics

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

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2018/07/PXD004334

PRIDE project URI

• PRIDE
  1. PXD004334
     1. Label: PRIDE project
     2. Name: Role for KDM3A in ciliogenesis