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@ARTICLE{Hansen:164661,
author = {Hansen, Jan N and Kaiser, Fabian and Leyendecker, Philipp
and Stüven, Birthe and Krause, Jens-Henning and
Derakhshandeh, Fatemeh and Irfan, Jaazba and Sroka, Tommy J
and Preval, Kenley M and Desai, Paurav B and Kraut, Michael
and Theis, Heidi and Drews, Anna-Dorothee and de Domenico,
Elena and Händler, Kristian and Pazour, Gregory J and
Henderson, David J P and Mick, David U and Wachten, Dagmar},
title = {{A} c{AMP} signalosome in primary cilia drives gene
expression and kidney cyst formation},
journal = {EMBO reports},
volume = {23},
number = {8},
issn = {1469-221X},
address = {Hoboken, NJ [u.a.]},
publisher = {Wiley},
reportid = {DZNE-2022-01191},
pages = {e54315},
year = {2022},
note = {(CC BY-NC-ND)},
abstract = {The primary cilium constitutes an organelle that
orchestrates signal transduction independently from the cell
body. Dysregulation of this intricate molecular architecture
leads to severe human diseases, commonly referred to as
ciliopathies. However, the molecular underpinnings how
ciliary signaling orchestrates a specific cellular output
remain elusive. By combining spatially resolved optogenetics
with RNA sequencing and imaging, we reveal a novel cAMP
signalosome that is functionally distinct from the
cytoplasm. We identify the genes and pathways targeted by
the ciliary cAMP signalosome and shed light on the
underlying mechanisms and downstream signaling. We reveal
that chronic stimulation of the ciliary cAMP signalosome
transforms kidney epithelia from tubules into cysts.
Counteracting this chronic cAMP elevation in the cilium by
small molecules targeting activation of phosphodiesterase-4
long isoforms inhibits cyst growth. Thereby, we identify a
novel concept of how the primary cilium controls cellular
functions and maintains tissue integrity in a specific and
spatially distinct manner and reveal novel molecular
components that might be involved in the development of one
of the most common genetic diseases, polycystic kidney
disease.},
keywords = {Cilia: metabolism / Cysts: metabolism / Gene Expression /
Humans / Kidney / Polycystic Kidney Diseases: genetics /
Polycystic Kidney Diseases: metabolism / CREB (Other) / PKD
(Other) / cAMP (Other) / optogenetics (Other) / primary
cilia (Other)},
cin = {AG Schultze / $R\&D$ PRECISE},
ddc = {570},
cid = {I:(DE-2719)1013031 / I:(DE-2719)5000031},
pnm = {354 - Disease Prevention and Healthy Aging (POF4-354)},
pid = {G:(DE-HGF)POF4-354},
typ = {PUB:(DE-HGF)16},
pmc = {pmc:PMC9346484},
pubmed = {pmid:35695071},
doi = {10.15252/embr.202154315},
url = {https://pub.dzne.de/record/164661},
}