PXD034412-1

PXD034412 is an original dataset announced via ProteomeXchange.

Title	TTC30A and TTC30B redundancy protects IFT complex B integrity and its pivotal role in ciliogenesis
Description	Intraflagellar transport (IFT) is a microtubule-based system that supports the assembly and maintenance of cilia, an essential organelle for development and maintenance of cellular integrity. Dysfunction of IFT was shown to lead to a wide spectrum of disease phenotypes, so called ciliopathies of variable severity. In previous studies two distinct complexes (IFT-A; IFT-B) were identified, containing multiple proteins that are part of the IFT machinery. Two of the IFT-B components are TTC30A and TTC30B and in contrast to all other IFT components, only these two are paralogues. To investigate whether these two proteins have a similar and essential ciliary or constitute redundant functions, CRIPSR/Cas9 was used to specifically knock-out TTC30A or B and to generate a double knock-out. Localization studies showed a redundancy of both proteins in ciliogenesis while polyglutamylation of cilia was affected by both single knockouts. Further, the localization of other IFT components was not affected by the depletion of a single paralogue. A loss of both proteins led to a severe ciliogenesis defect, resulting in no cilia formation which can be rescued by expression of TTC30A or B. The redundancy can be explained by highly similar interaction patterns of both paralogues, both equally interact with the IFT-B machinery. In summary our study demonstrates that a loss of one TTC30 paralogue can mostly compensate severe ciliary defects, due to redundancy. However, cells assemble shorter cilia which are potentially limited in their functions, especially because of impaired polyglutamylation. A complete loss of both proteins leads to a deficit in IFT complex B integrity followed by disrupted IFT and subsequently no cilia formation
HostingRepository	PRIDE
AnnounceDate	2022-08-12
AnnouncementXML	Submission_2022-08-11_22:02:08.392.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	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2022-06-09 08:34:39	ID requested
⏵ 1	2022-08-11 22:02:09	announced

Hoffmann F, Bolz S, Junger K, Klose F, Schubert T, Woerz F, Boldt K, Ueffing M, Beyer T, TTC30A and TTC30B Redundancy Protects IFT Complex B Integrity and Its Pivotal Role in Ciliogenesis. Genes (Basel), 13(7):(2022) [pubmed]

submitter keyword: cilia, IFT-B, TTC30

Dr. Tina Beyer
contact affiliation	Eberhard Karls University Tübingen, Institute for Ophthalmic Research
contact email	Tina.Beyer@uni-tuebingen.de
lab head
Tina Beyer
contact affiliation	Uniklinik Tübingen
contact email	Tina.Beyer@uni-tuebingen.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD034412
     1. Label: PRIDE project
     2. Name: TTC30A and TTC30B redundancy protects IFT complex B integrity and its pivotal role in ciliogenesis