PXD046401

PXD046401 is an original dataset announced via ProteomeXchange.

Title	Interactome analysis reveals a link of the novel ALMS1-CEP70 complex to centrosomal clusters
Description	Alström syndrome (ALMS) is a very rare autosomal-recessive disorder, causing a broad range of clinical defects most notably retinal degeneration, type 2 diabetes and truncal obesity. The ALMS1 gene codes for a ~0.5 MDa protein, which has hampered analysis in the past. Interestingly, ALMS1 has been shown to localize at the centrioles and basal body of cilia, and is involved in signaling processes, e.g. TGF-β signaling. However, the exact molecular function of ALMS1 at the basal body is still elusive and controversial. We recently demonstrated that protein complex analysis utilizing endogenously tagged cells provides an excellent tool to investigate protein interactions of ciliary proteins. Here, CRISPR/Cas9-mediated endogenously tagged ALMS1 cells were used for affinity-based protein complex analysis. Centrosomal and microtubule-associated proteins were identified, which are potential regulators of ALMS1 function, like the centrosomal protein 70 kDa (CEP70). Candidate proteins were further investigated in ALMS1 deficient hTERT-RPE1 cells. Loss of ALMS1 led to shortened cilia with no change in structural protein localization, e.g. acetylated and ɣ-tubulin, Centrin-3 or the novel interactor CEP70. On the other hand, reduction of CEP70 resulted in decreased ALMS1 at the ciliary basal body. Complex analysis of CEP70 revealed domain-specific ALMS1 interaction involving the TPR-containing C-terminal (TRP-CT) fragment of CEP70. In addition to ALMS1, several ciliary proteins, including CEP135, were found to specifically bind to the TPR-CT domain. Data are available via ProteomeXchange with identifier PXD042621. Protein interactors identified in this study provide candidate lists, which help to understand ALMS1 and CEP70 function in cilia-related protein modification, cell death, and disease-related mechanisms.
HostingRepository	PRIDE
AnnounceDate	2024-01-25
AnnouncementXML	Submission_2024-01-25_14:21:05.940.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Tina Beyer
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive; Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2023-10-25 15:02:30	ID requested
⏵ 1	2024-01-25 14:21:06	announced

10.1016/J.MCPRO.2023.100701;

submitter keyword: cilia, centrosome, basal body, ciliopathy,Alström syndrome, CRISPR/Cas9, protein complex analysis

Dr. Karsten Boldt
contact affiliation	Institute for Ophthalmic Research University of Tübingen
contact email	karsten.boldt@uni-tuebingen.de
lab head
Tina Beyer
contact affiliation	Uniklinik Tübingen
contact email	Tina.Beyer@uni-tuebingen.de
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/2024/01/PXD046401

PRIDE project URI

• PRIDE
  1. PXD046401
     1. Label: PRIDE project
     2. Name: Interactome analysis reveals a link of the novel ALMS1-CEP70 complex to centrosomal clusters