ATMIN is a transcriptional regulator of both lung morphogenesis and ciliogenesis
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
Stevens, Jonathan L
Grimes, Daniel T
Patel, Saloni H
Morthorst, Stine K
Williams, Debbie J
Khoronenkova, Svetlana V
Esapa, Chris T
Dianov, Grigory L
Johnson, Colin A
Pedersen, Lotte B
Norris, Dominic P
MetadataShow full item record
AbstractInitially identified in DNA damage repair, ATM-interactor (ATMIN) further functions as a transcriptional regulator of lung morphogenesis. Here we analyse three mouse mutants, Atmin(gpg6/gpg6), Atmin(H210Q/H210Q) and Dynll1(GT/GT), revealing how ATMIN and its transcriptional target dynein light chain LC8-type 1 (DYNLL1) are required for normal lung morphogenesis and ciliogenesis. Expression screening of ciliogenic genes confirmed Dynll1 to be controlled by ATMIN and further revealed moderately altered expression of known intraflagellar transport (IFT) protein-encoding loci in Atmin mutant embryos. Significantly, Dynll1(GT/GT) embryonic cilia exhibited shortening and bulging, highly similar to the characterised retrograde IFT phenotype of Dync2h1. Depletion of ATMIN or DYNLL1 in cultured cells recapitulated the in vivo ciliogenesis phenotypes and expression of DYNLL1 or the related DYNLL2 rescued the effects of loss of ATMIN, demonstrating that ATMIN primarily promotes ciliogenesis by regulating Dynll1 expression. Furthermore, DYNLL1 as well as DYNLL2 localised to cilia in puncta, consistent with IFT particles, and physically interacted with WDR34, a mammalian homologue of the Chlamydomonas cytoplasmic dynein 2 intermediate chain that also localised to the cilium. This study extends the established Atmin-Dynll1 relationship into a developmental and a ciliary context, uncovering a novel series of interactions between DYNLL1, WDR34 and ATMIN. This identifies potential novel components of cytoplasmic dynein 2 and furthermore provides fresh insights into the molecular pathogenesis of human skeletal ciliopathies.
PublisherCompany of Biologists
SponsorsMedical Research Council
- LC8 dynein light chain (DYNLL1) binds to the C-terminal domain of ATM-interacting protein (ATMIN/ASCIZ) and regulates its subcellular localization.
- Authors: Rapali P, García-Mayoral MF, Martínez-Moreno M, Tárnok K, Schlett K, Albar JP, Bruix M, Nyitray L, Rodriguez-Crespo I
- Issue date: 2011 Oct 28
- Atmin mediates kidney morphogenesis by modulating Wnt signaling.
- Authors: Goggolidou P, Hadjirin NF, Bak A, Papakrivopoulou E, Hilton H, Norris DP, Dean CH
- Issue date: 2014 Oct 15
- Loss of dynein-2 intermediate chain Wdr34 results in defects in retrograde ciliary protein trafficking and Hedgehog signaling in the mouse.
- Authors: Wu C, Li J, Peterson A, Tao K, Wang B
- Issue date: 2017 Jul 1
- Mutations in the gene encoding IFT dynein complex component WDR34 cause Jeune asphyxiating thoracic dystrophy.
- Authors: Schmidts M, Vodopiutz J, Christou-Savina S, Cortés CR, McInerney-Leo AM, Emes RD, Arts HH, Tüysüz B, D'Silva J, Leo PJ, Giles TC, Oud MM, Harris JA, Koopmans M, Marshall M, Elçioglu N, Kuechler A, Bockenhauer D, Moore AT, Wilson LC, Janecke AR, Hurles ME, Emmet W, Gardiner B, Streubel B, Dopita B, Zankl A, Kayserili H, Scambler PJ, Brown MA, Beales PL, Wicking C, UK10K., Duncan EL, Mitchison HM
- Issue date: 2013 Nov 7
- ATM substrate Chk2-interacting Zn2+ finger (ASCIZ) Is a bi-functional transcriptional activator and feedback sensor in the regulation of dynein light chain (DYNLL1) expression.
- Authors: Jurado S, Conlan LA, Baker EK, Ng JL, Tenis N, Hoch NC, Gleeson K, Smeets M, Izon D, Heierhorst J
- Issue date: 2012 Jan 27