Oct 24, 2018

The Heterotaxy Gene, CCDC11, is Essential for Cytokinesis and Cell-Cell Adhesion Via RhoA Regulation

BioRxiv : the Preprint Server for Biology
Saurabh S KulkarniMustafa K Khokha

Abstract

Mutations in CCDC11 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's phenotype. Upon ccdc11 depletion, normally monociliated cells of the Left-Right Organizer (LRO) exhibit multiple cilia per cell. Unexpectedly, we found that ccdc11 is necessary for successful cytokinesis, and the multiciliation observed in ccdc11-depleted cells was due to failed cytokinesis. Furthermore, ccdc11 depletion alters cell-cell adhesion with a reduction in the junctional localization of adhesion molecules. The small GTPase RhoA is critical for cytokinesis and cell-cell adhesion. Because the ccdc11 depletion phenotypes are reminiscent of RhoA loss of function, we investigated a possible connection to the regulation of RhoA signaling. We demonstrate that CCDC11 is localized to the cytokinetic contractile ring overlapping with RhoA during cytokinesis and regulates total RhoA protein levels. Our results suggest that CCDC11 connects cytokinesis and LR patterning via RhoA regulation, providing a potential mechanism for heterotaxy disease pathogenesis.

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Mentioned in this Paper

Pathogenic Aspects
Pathogenesis
CCDC11 protein, human
Regulation of Biological Process
Leptin receptor
CFAP53
Cytokinesis of the Fertilized Ovum
Gene Mutation
Organ
Eyelash

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