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@ARTICLE{Boldt:138561,
author = {Boldt, Karsten and van Reeuwijk, Jeroen and Lu, Qianhao and
Koutroumpas, Konstantinos and Nguyen, Thanh-Minh T and
Texier, Yves and van Beersum, Sylvia E C and Horn, Nicola
and Willer, Jason R and Mans, Dorus A and Dougherty, Gerard
and Lamers, Ideke J C and Coene, Karlien L M and Arts,
Heleen H and Betts, Matthew J and Beyer, Tina and Bolat,
Emine and Gloeckner, Christian Johannes and Haidari, Khatera
and Hetterschijt, Lisette and Iaconis, Daniela and Jenkins,
Dagan and Klose, Franziska and Knapp, Barbara and Latour,
Brooke and Letteboer, Stef J F and Marcelis, Carlo L and
Mitic, Dragana and Morleo, Manuela and Oud, Machteld M and
Riemersma, Moniek and Rix, Susan and Terhal, Paulien A and
Toedt, Grischa and van Dam, Teunis J P and de Vrieze, Erik
and Wissinger, Yasmin and Wu, Ka Man and Apic, Gordana and
Beales, Philip L and Blacque, Oliver E and Gibson, Toby J
and Huynen, Martijn A and Katsanis, Nicholas and Kremer,
Hannie and Omran, Heymut and van Wijk, Erwin and Wolfrum,
Uwe and Kepes, François and Davis, Erica E and Franco,
Brunella and Giles, Rachel H and Ueffing, Marius and
Russell, Robert B and Roepman, Ronald and Group, UK10K Rare
Diseases and Al-Turki, Saeed and Anderson, Carl and Antony,
Dinu and Barroso, Inês and Bentham, Jamie and Bhattacharya,
Shoumo and Carss, Keren and Chatterjee, Krishna and Cirak,
Sebahattin and Cosgrove, Catherine and Danecek, Petr and
Durbin, Richard and Fitzpatrick, David and Floyd, Jamie and
Reghan Foley, A. and Franklin, Chris and Futema, Marta and
Humphries, Steve E and Hurles, Matt and Joyce, Chris and
McCarthy, Shane and Mitchison, Hannah M and Muddyman, Dawn
and Muntoni, Francesco and O'Rahilly, Stephen and
Onoufriadis, Alexandros and Payne, Felicity and Plagnol,
Vincent and Raymond, Lucy and Savage, David B and Scambler,
Peter and Schmidts, Miriam and Schoenmakers, Nadia and
Semple, Robert and Serra, Eva and Stalker, Jim and van
Kogelenberg, Margriet and Vijayarangakannan, Parthiban and
Walter, Klaudia and Whittall, Ros and Williamson, Kathy},
title = {{A}n organelle-specific protein landscape identifies novel
diseases and molecular mechanisms.},
journal = {Nature Communications},
volume = {7},
number = {1},
issn = {2041-1723},
address = {[London]},
publisher = {Nature Publishing Group UK},
reportid = {DZNE-2020-04883},
pages = {11491},
year = {2016},
abstract = {Cellular organelles provide opportunities to relate
biological mechanisms to disease. Here we use affinity
proteomics, genetics and cell biology to interrogate cilia:
poorly understood organelles, where defects cause genetic
diseases. Two hundred and seventeen tagged human ciliary
proteins create a final landscape of 1,319 proteins, 4,905
interactions and 52 complexes. Reverse tagging, repetition
of purifications and statistical analyses, produce a
high-resolution network that reveals organelle-specific
interactions and complexes not apparent in larger studies,
and links vesicle transport, the cytoskeleton, signalling
and ubiquitination to ciliary signalling and proteostasis.
We observe sub-complexes in exocyst and intraflagellar
transport complexes, which we validate biochemically, and by
probing structurally predicted, disruptive, genetic variants
from ciliary disease patients. The landscape suggests other
genetic diseases could be ciliary including 3M syndrome. We
show that 3M genes are involved in ciliogenesis, and that
patient fibroblasts lack cilia. Overall, this
organelle-specific targeting strategy shows considerable
promise for Systems Medicine.},
keywords = {Biological Transport: physiology / Chromatography,
Affinity: methods / Cilia: metabolism / Ciliopathies:
genetics / Ciliopathies: pathology / Ciliopathies: therapy /
DNA Mutational Analysis / Datasets as Topic / Dwarfism:
genetics / Dwarfism: pathology / Dwarfism: therapy /
Fibroblasts / HEK293 Cells / Humans / Mass Spectrometry /
Molecular Targeted Therapy: methods / Muscle Hypotonia:
genetics / Muscle Hypotonia: pathology / Muscle Hypotonia:
therapy / Protein Interaction Mapping: methods / Protein
Interaction Maps / Proteins: genetics / Proteins: isolation
$\&$ purification / Proteins: metabolism / Proteomics:
methods / Spine: abnormalities / Spine: pathology / Systems
Analysis / Proteins (NLM Chemicals)},
cin = {AG Gloeckner},
ddc = {500},
cid = {I:(DE-2719)1210007},
pnm = {345 - Population Studies and Genetics (POF3-345)},
pid = {G:(DE-HGF)POF3-345},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:27173435},
pmc = {pmc:PMC4869170},
doi = {10.1038/ncomms11491},
url = {https://pub.dzne.de/record/138561},
}