The Heterotaxy Gene CCDC11 Is Important for Cytokinesis via RhoA Regulation

Saurabh S Kulkarni, Rachel E Stephenson, Sarah Amalraj, Angelo Arrigo, Ewelina Betleja, James J Moresco, John R Yates, Moe R Mahjoub, Ann L Miller, Mustafa K Khokha

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
JournalCytoskeleton
DOIs
StateAccepted/In press - 2024

Keywords

  • CFAP53
  • cilia
  • congenital heart disease
  • cytokinesis
  • left–right patterning
  • RhoA
  • Xenopus

Fingerprint

Dive into the research topics of 'The Heterotaxy Gene CCDC11 Is Important for Cytokinesis via RhoA Regulation'. Together they form a unique fingerprint.

Cite this