C2orf62 and TTC17 are involved in actin organization and ciliogenesis in zebrafish and human.
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.
Department of Human Protein Sciences, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
Franck
F
Bontems
Department of Genetic Medicine and Development, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
Richard J
RJ
Fish
Department of Human Protein Sciences, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
Irene
I
Borlat
CRCM - Inserm U1068, Marseille, France ; Institut Paoli-Calmettes, Marseille, France ; CNRS UMR7258, Marseille, France ; Aix-Marseille University, Marseille, France.
Frédérique
F
Lembo
IRSET - Inserm U1085, Rennes, France.
Sophie
S
Chocu
IRSET - Inserm U1085, Rennes, France.
Frédéric
F
Chalmel
CRCM - Inserm U1068, Marseille, France ; Institut Paoli-Calmettes, Marseille, France ; CNRS UMR7258, Marseille, France ; Aix-Marseille University, Marseille, France.
Jean-Paul
JP
Borg
IRSET - Inserm U1085, Rennes, France.
Charles
C
Pineau
Department of Genetic Medicine and Development, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
Marguerite
M
Neerman-Arbez
Department of Human Protein Sciences, Faculty of Medicine, University of Geneva, Geneva, Switzerland ; SIB-Swiss Institute of Bioinformatics, Geneva, Switzerland.
Amos
A
Bairoch
Department of Human Protein Sciences, Faculty of Medicine, University of Geneva, Geneva, Switzerland ; SIB-Swiss Institute of Bioinformatics, Geneva, Switzerland.
Lydie
L
Lane
D000199:Actins / Q000502:physiology*; D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002923:Cilia / Q000235:genetics / Q000502:physiology*; D019295:Computational Biology; D003598:Cytoskeletal Proteins; D017931:DNA Primers / Q000235:genetics; D031541:Fluorescence Resonance Energy Transfer; D020869:Gene Expression Profiling; D055785:Gene Knockdown Techniques; D049452:Green Fluorescent Proteins; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008164:Luminescent Proteins; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016415:Sequence Alignment; D020798:Two-Hybrid System Techniques; D015027:Zebrafish / Q000235:genetics*; D000097573:Red Fluorescent Protein
D000199:Actins; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D017931:DNA Primers; D049452:Green Fluorescent Proteins; D008164:Luminescent Proteins; D000097573:Red Fluorescent Protein; C000592858:CATIP protein, human; C485184:enhanced green fluorescent protein; C000592857:tetratricopeptide repeat protein 17, human