OFIP/KIAA0753 forms a complex with OFD1 and FOR20 at pericentriolar satellites and centrosomes and is mutated in one individual with oral-facial-digital syndrome.

Abstract

Oral-facial-digital (OFD) syndromes are rare heterogeneous disorders characterized by the association of abnormalities of the face, the oral cavity and the extremities, some due to mutations in proteins of the transition zone of the primary cilia or the closely associated distal end of centrioles. These two structures are essential for the formation of functional cilia, and for signaling events during development. We report here causal compound heterozygous mutations of KIAA0753/OFIP in a patient with an OFD VI syndrome. We show that the KIAA0753/OFIP protein, whose sequence is conserved in ciliated species, associates with centrosome/centriole and pericentriolar satellites in human cells and forms a complex with FOR20 and OFD1. The decreased expression of any component of this ternary complex in RPE1 cells causes a defective recruitment onto centrosomes and satellites. The OFD KIAA0753/OFIP mutant loses its capacity to interact with FOR20 and OFD1, which may be the molecular basis of the defect. We also show that KIAA0753/OFIP has microtubule-stabilizing activity. OFD1 and FOR20 are known to regulate the integrity of the centriole distal end, confirming that this structural element is a target of importance for pathogenic mutations in ciliopathies.

DOI: 10.1093/hmg/ddv488
0500100020162017
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@article{Chevrier2016OFIPKIAA0753FA, title={OFIP/KIAA0753 forms a complex with OFD1 and FOR20 at pericentriolar satellites and centrosomes and is mutated in one individual with oral-facial-digital syndrome.}, author={V{\'e}ronique Gogniat Chevrier and A Bruel and Teunis J. P. van Dam and Brunella Franco and Melissa Lo Scalzo and Fr{\'e}d{\'e}rique Lembo and St{\'e}phane Audebert and Emilie Baudelet and Daniel Isnardon and Ang{\'e}lique Bole and Jean-Paul Borg and Paul Kuentz and Julien Thevenon and Lydie Burglen and Laurence Olivier Faivre and Jean-Baptiste de la Rivi{\`e}re and Martijn A. Huynen and Daniel Birnbaum and Olivier Rosnet and Christel Thauvin-Robinet}, journal={Human molecular genetics}, year={2016}, volume={25 3}, pages={497-513} }