C2orf62 and TTC17 are involved in actin organization and ciliogenesis in zebrafish and human

Franck Bontems; Richard J Fish; Irene Borlat; Frédérique Lembo; Sophie Chocu; Frédéric Chalmel; Jean-Paul Borg; Charles Pineau; Marguerite Neerman-Arbez; Amos Bairoch; Lydie Lane

doi:10.1371/journal.pone.0086476

C2orf62 and TTC17 are involved in actin organization and ciliogenesis in zebrafish and human

PLoS One. 2014 Jan 27;9(1):e86476. doi: 10.1371/journal.pone.0086476. eCollection 2014.

Authors

Affiliations

¹ Department of Human Protein Sciences, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
² Department of Genetic Medicine and Development, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
³ CRCM - Inserm U1068, Marseille, France ; Institut Paoli-Calmettes, Marseille, France ; CNRS UMR7258, Marseille, France ; Aix-Marseille University, Marseille, France.
⁴ IRSET - Inserm U1085, Rennes, France.
⁵ Department of Human Protein Sciences, Faculty of Medicine, University of Geneva, Geneva, Switzerland ; SIB-Swiss Institute of Bioinformatics, Geneva, Switzerland.

Abstract

Vertebrate genomes contain around 20,000 protein-encoding genes, of which a large fraction is still not associated with specific functions. A major task in future genomics will thus be to assign physiological roles to all open reading frames revealed by genome sequencing. Here we show that C2orf62, a highly conserved protein with little homology to characterized proteins, is strongly expressed in testis in zebrafish and mammals, and in various types of ciliated cells during zebrafish development. By yeast two hybrid and GST pull-down, C2orf62 was shown to interact with TTC17, another uncharacterized protein. Depletion of either C2orf62 or TTC17 in human ciliated cells interferes with actin polymerization and reduces the number of primary cilia without changing their length. Zebrafish embryos injected with morpholinos against C2orf62 or TTC17, or with mRNA coding for the C2orf62 C-terminal part containing a RII dimerization/docking (R2D2) - like domain show morphological defects consistent with imperfect ciliogenesis. We provide here the first evidence for a C2orf62-TTC17 axis that would regulate actin polymerization and ciliogenesis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Actins / physiology*
Animals
Base Sequence
Carrier Proteins / genetics
Carrier Proteins / metabolism*
Cell Line
Cilia / genetics
Cilia / physiology*
Computational Biology
Cytoskeletal Proteins
DNA Primers / genetics
Fluorescence Resonance Energy Transfer
Gene Expression Profiling
Gene Knockdown Techniques
Green Fluorescent Proteins
Humans
Immunohistochemistry
In Situ Hybridization
Luminescent Proteins
Real-Time Polymerase Chain Reaction
Red Fluorescent Protein
Reverse Transcriptase Polymerase Chain Reaction
Sequence Alignment
Two-Hybrid System Techniques
Zebrafish / genetics*

Substances

Actins
CATIP protein, human
Carrier Proteins
Cytoskeletal Proteins
DNA Primers
Luminescent Proteins
enhanced green fluorescent protein
tetratricopeptide repeat protein 17, human
Green Fluorescent Proteins

Grants and funding

JPB’s lab is supported by La Ligue Contre le Cancer (Label Ligue 2010), EUCAAD (FP7 program), and Institut Paoli-Calmettes. AB’s lab is supported by the Faculty of Medicine of the University of Geneva. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.