PXD078750

PXD078750 is an original dataset announced via ProteomeXchange.

Title	ZDHHC5 interacts physically and functionally with DLG1 at primary cilia and regulates ciliary length and kidney morphology
Description	We recently identified a role for the Scribble polarity complex protein DLG1 in regulating the protein composition, and in some cases the length, of primary cilia in mouse kidney epithelial cells. We also reported that palmitoyl transferase ZDHHC5 localizes to primary cilia in such cells and negatively regulates their length. In the present study, we generated mouse inner medullary collecting duct (IMCD3) cell lines stably expressing DLG1-BioID2 and performed proximity labeling proteomics in ciliated cells to identify putative cilium-associated DLG1 interactors. We identified 46 high-confidence DLG1-BioID2 proximity interactors, 35 of which had been previously detected in diverse ciliary proteomes and/or shown to physically associate with ciliary or centrosomal proteins. These included ZDHHC5, whose interaction with DLG1 was confirmed by immunoprecipitation. AlphaFold modelling suggested a direct interaction between DLG1 and ZDHHC5, whereas quantitative immunofluorescence microscopy confirmed that ZDHHC5 localizes to primary cilia, most likely independently of DLG1. Similar experiments showed that DLG1 also binds SCAMP3 and STXBP1 and is required for proper localization of STXBP1 at the ciliary base. Additionally, depletion of zdhhc5a and zdhhc5b in zebrafish led to ciliopathy-like phenotypes, including brain edema, curved tail and significantly enlarged glomerular area, which was accompanied by significantly elongated cilia in the brain and pronephros. Together, these findings strengthen and extend previous evidence linking DLG1, ZDHHC5 and STXBP1 to primary cilia and suggest that DLG1 may regulate ciliary length and function in kidney epithelial cells through physical interactions with ZDHHC5 and STXBP1.
HostingRepository	MassIVE
AnnounceDate	2026-05-22
AnnouncementXML	Submission_2026-05-22_15:22:46.016.xml
DigitalObjectIdentifier
ReviewLevel	Non peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Karsten Boldt
SpeciesList	scientific name: mus musculus;
ModificationList	Oxidation; Carbamidomethyl
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2026-05-22 14:03:31	ID requested
⏵ 1	2026-05-22 15:22:46	announced

no publication

submitter keyword: DLG1, proximity labelling, primary cilia, ZDHHC5, DatasetType:Proteomics

Karsten Boldt
contact affiliation	Eberhard-Karls Universitaet Tuebingen
contact email	karsten.boldt@uni-tuebingen.de
lab head
Karsten Boldt
contact affiliation	Eberhard-Karls Universit?t T?bingen
contact email	karsten.boldt@uni-tuebingen.de
dataset submitter

MassIVE dataset URI

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