Journal Article

DZNE-2022-01191

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png A cAMP signalosome in primary cilia drives gene expression and kidney cyst formation

Hansen, J. N. ; Kaiser, F. ; Leyendecker, P. ; Stüven, B. ; Krause, J.-H. ; Derakhshandeh, F. ; Irfan, J. ; Sroka, T. J. ; Preval, K. M. ; Desai, P. B. ; Kraut, M.DZNE* ; Theis, H.DZNE* ; Drews, A.-D.DZNE* ; de Domenico, E.DZNE* ; Händler, K.DZNE* ; Pazour, G. J. ; Henderson, D. J. P. ; Mick, D. U. ; Wachten, D.

2022
Wiley Hoboken, NJ [u.a.]

This record in other databases:    

Please use a persistent id in citations: doi:10.15252/embr.202154315

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.

Keyword(s): Cilia: metabolism (MeSH) ; Cysts: metabolism (MeSH) ; Gene Expression (MeSH) ; Humans (MeSH) ; Kidney (MeSH) ; Polycystic Kidney Diseases: genetics (MeSH) ; Polycystic Kidney Diseases: metabolism (MeSH) ; CREB ; PKD ; cAMP ; optogenetics ; primary cilia

Note: (CC BY-NC-ND)

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Contributing Institute(s):

1. United epigenomic platform (AG Schultze)
2. Platform for Single Cell Genomics and Epigenomics at DZNE & University of Bonn (R&D PRECISE)

Research Program(s):

1. 354 - Disease Prevention and Healthy Aging (POF4-354) (POF4-354)

Appears in the scientific report 2022

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Database coverage:
; ; ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; DEAL Wiley ; Essential Science Indicators ; IF >= 5 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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