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

  title={The Heterotaxy Gene CCDC11 is Essential for Cytokinesis and Cell-Cell Adhesion via RhoA Regulation},
  author={Saurabh S Kulkarni and Rachel E. Stephenson and S. F. A. Amalraj and Ewelina Betleja and James J. Moresco and John R. Yates and Moe R Mahjoub and Ann L. Miller and Mustafa K. Khokha},
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 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… Expand
2 Citations
Xenopus to the rescue: A model to validate and characterize candidate ciliopathy genes
Xenopus, a genetically tractable and high‐throughput vertebrate model, has played a central role in identifying, validating, and characterizing candidate ciliopathy genes and is considered a powerful model to improve the understanding of the underlying disease mechanisms and explain the patient phenotype. Expand
Mechanical stretch scales centriole number to apical area via Piezo1 in multiciliated cells
Mechanical forces calibrate cilia/centriole number to the MCC apical area via Piezo1, a mechanosensitive ion channel, suggesting a potential role in centriole amplification. Expand


Roles of the cilium-associated gene CCDC11 in left-right patterning and in laterality disorders in humans.
The roles of CCDC11 and the implications of the identified mutation on left-right axial patterning in patient-derived cells and in the frog embryo as a model organism are characterized. Expand
Mutations in CCDC11, which Encodes a Coiled‐Coil Containing Ciliary Protein, Causes Situs Inversus Due to Dysmotility of Monocilia in the Left–Right Organizer
It is demonstrated that CCDC11 has a conserved essential function in cilia of the vertebrate LR organizer, which is the first ciliary component, which has a differential localization and function in different kinds of motile cilia. Expand
The Heterotaxy gene, GALNT11, glycosylates Notch to orchestrate cilia type and laterality
It is demonstrated that Galnt11 modifies Notch, establishing an essential balance between motile and immotile cilia at the left–right organizer to determine laterality, and reveal a novel mechanism for human heterotaxy. Expand
Xenopus laevis nucleotide binding protein 1 (xNubp1) is important for convergent extension movements and controls ciliogenesis via regulation of the actin cytoskeleton.
It is shown that xNubp1 is expressed maternally, displays elevated expression in neural tissues and is required for convergent extension movements and neural tube closure, and that problems in basal body transport in xNUBp1 morphants are associated with defects of the internal network of actin, while spacing and polarity issues are due to a failure of the apical and sub-apical actin pools to mature into a network. Expand
Shared mechanisms regulate spatiotemporal RhoA-dependent actomyosin contractility during adhesion and cell division
The functional differences and similarities of the different RhoA-associated factors that have been linked to both the regulation of cell-cell adhesion and cytokinesis are highlighted. Expand
A role for central spindle proteins in cilia structure and function
It is shown that several central spindle/midbody proteins (PRC1, MKLP‐1, INCENP, centriolin) also localize in specific patterns at the basal body complex in vertebrate ciliated epithelial cells, suggesting the conserved reuse of a surprisingly large number of proteins in the cytokinetic apparatus and in cilia. Expand
The cilia protein IFT88 is required for spindle orientation in mitosis
It is shown that IFT88 depletion induces mitotic defects in human cultured cells, in kidney cells from the IFT 88 mouse mutant Tg737orpk and in zebrafish embryos, and has important implications for the etiology of ciliopathies. Expand
Intraflagellar transport (IFT) role in ciliary assembly, resorption and signalling.
An overview of ciliogenesis with particular emphasis on the molecular mechanisms and functions of intraflagellar transport (IFT), a bidirectional transport system that tracks along the polarized microtubules of the axoneme and which is required for assembly of almost all cilia and flagella. Expand
IFT88 plays a cilia- and PCP-independent role in controlling oriented cell divisions during vertebrate embryonic development.
It is clearly demonstrate that cilia are not required to establish PCP and rather, IFT88 plays a cilia-independent role in controlling oriented cell divisions at gastrulation and neurulation. Expand
Rho localization in cells and tissues.
In mammalian cultured cells and tissues through evaluation of anti-Rho antibodies and fixation protocols, Rho localization differed depending on cell type, probably reflecting the functional differences of each cell type. Expand