PXD019806

PXD019806 is an original dataset announced via ProteomeXchange.

Title	CFAP45 deficiency causes situs abnormalities and asthenospermia by disrupting an axonemal adenine nucleotide homeostasis module
Description	Axonemal dynein ATPases direct eukaryotic ciliary and flagellar beating via adenosine triphosphate (ATP) hydrolysis. The modulatory effect of adenosine monophosphate (AMP) and adenosine diphosphate (ADP) on flagellar beating is not fully understood. Here we describe a deficiency of CFAP45 in both humans and mice that presents a motile ciliopathy featuring situs inversus totalis and asthenospermia. CFAP45-deficient cilia and flagella show normal morphology and axonemal ultrastructure. Proteomic profiling links CFAP45 to an axonemal module including dynein ATPases and adenylate kinase as well as CFAP52, whose mutations cause a similar human ciliopathy. CFAP45 binds AMP in vitro, consistent with structural modelling that identifies an AMP-binding interface between CFAP45 and AK8. Microtubule sliding of dyskinetic sperm from Cfap45-/- mice is partially rescued with the addition of either AMP or ADP with ATP, compared to ATP alone. We propose that CFAP45 supports mammalian ciliary and flagellar beating via an adenine nucleotide homeostasis module.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_05:14:36.308.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Karsten Boldt
SpeciesList	scientific name: Sus scrofa domesticus (domestic pig); NCBI TaxID: 9825;
ModificationList	acetylated residue; iodoacetamide derivatized residue
Instrument	LTQ Orbitrap

Revision	Datetime	Status	ChangeLog Entry
0	2020-06-16 08:30:22	ID requested
1	2020-11-04 23:23:45	announced
⏵ 2	2024-10-22 05:14:37	announced	2024-10-22: Updated project metadata.

10.1038/s41467-020-19113-0;

Dougherty GW, Mizuno K, N, ö, the-Menchen T, Ikawa Y, Boldt K, Ta-Shma A, Aprea I, Minegishi K, Pang YP, Pennekamp P, Loges NT, Raidt J, Hjeij R, Wallmeier J, Mussaffi H, Perles Z, Elpeleg O, Rabert F, Shiratori H, Letteboer SJ, Horn N, Young S, Str, ü, nker T, Stumme F, Werner C, Olbrich H, Takaoka K, Ide T, Twan WK, Biebach L, Gro, ß, e-Onnebrink J, Klinkenbusch JA, Praveen K, Bracht DC, H, ö, ben IM, Junger K, G, ü, tzlaff J, Cindri, ć S, Aviram M, Kaiser T, Memari Y, Dzeja PP, Dworniczak B, Ueffing M, Roepman R, Bartscherer K, Katsanis N, Davis EE, Amirav I, Hamada H, Omran H, CFAP45 deficiency causes situs abnormalities and asthenospermia by disrupting an axonemal adenine nucleotide homeostasis module. Nat Commun, 11(1):5520(2020) [pubmed]

submitter keyword: motile cilia, protein complexes,CFAP45

Dr. Karsten Boldt
contact affiliation	Medical Bioanalytics Institute for Ophthalmic Research Eberhard-Karls-University Tuebingen
contact email	karsten.boldt@uni-tuebingen.de
lab head
Karsten Boldt
contact affiliation	Medical Bioanalytics
contact email	karsten.boldt@uni-tuebingen.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD019806
     1. Label: PRIDE project
     2. Name: CFAP45 deficiency causes situs abnormalities and asthenospermia by disrupting an axonemal adenine nucleotide homeostasis module