The Heterotaxy Gene CCDC11 Is Important for Cytokinesis via RhoA Regulation.
Xenopus
CFAP53
RhoA
cilia
congenital heart disease
cytokinesis
left–right patterning
Journal
Cytoskeleton (Hoboken, N.J.)
ISSN: 1949-3592
Titre abrégé: Cytoskeleton (Hoboken)
Pays: United States
ID NLM: 101523844
Informations de publication
Date de publication:
31 Oct 2024
31 Oct 2024
Historique:
revised:
10
10
2024
received:
23
10
2023
accepted:
15
10
2024
medline:
31
10
2024
pubmed:
31
10
2024
entrez:
31
10
2024
Statut:
aheadofprint
Résumé
Mutations in CCDC11 (cfap53) have been identified in multiple patients with heterotaxy (Htx), a disorder of left-right (LR) patterning of the internal organs. In Xenopus, depletion of Ccdc11 causes defects in LR patterning, recapitulating the patient phenotype. Upon Ccdc11 depletion, monociliated cells of the Left-Right Organizer (LRO) exhibit multiple cilia per cell. Unexpectedly, we found that Ccdc11 is necessary for successful cytokinesis, explaining the multiciliation phenotype observed in Ccdc11-depleted cells. The small GTPase RhoA is critical for cytokinesis, and our Ccdc11 depletion phenotypes are reminiscent of RhoA loss of function. Here, we demonstrate that during cytokinesis CCDC11 is localized to the cytokinetic contractile ring overlapping with RhoA, and CCDC11 regulates total RhoA protein levels. Our results connect CCDC11 to cytokinesis and LR patterning via RhoA regulation, providing a potential mechanism for heterotaxy disease pathogenesis.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NHLBI NIH HHS
ID : 5K99HL133606
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01-HL128370
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01-DK108005
Pays : United States
Organisme : National Institute of Child Health and Human Development
ID : R01HD081379
Organisme : NIGMS NIH HHS
ID : P41 GM103533
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01GM112794
Pays : United States
Organisme : National Science Foundation Graduate Research Fellowship
ID : DGE #1256260
Informations de copyright
© 2024 The Author(s). Cytoskeleton published by Wiley Periodicals LLC.
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