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.

Date publication

février 2016

Journal

Human molecular genetics

Auteurs

Membres identifiés du Cancéropôle Est :
Pr FAIVRE Laurence , Pr KUENTZ Paul

Tous les auteurs :
Chevrier V, Bruel AL, Van Dam TJ, Franco B, Lo Scalzo M, Lembo F, Audebert S, Baudelet E, Isnardon D, Bole A, Borg JP, Kuentz P, Thevenon J, Burglen L, Faivre L, Rivière JB, Huynen MA, Birnbaum D, Rosnet O, Thauvin-Robinet C

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/26643951

Résumé

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.

Mots clés

Amino Acid Sequence, Base Sequence, Centrioles, metabolism, Centrosome, metabolism, Cilia, genetics, Conserved Sequence, Female, Gene Expression, Heterozygote, Humans, Infant, Newborn, Microtubule-Associated Proteins, genetics, Molecular Sequence Data, Mutation, Orofaciodigital Syndromes, genetics, Protein Binding, Proteins, genetics, Sequence Alignment

Référence

Hum. Mol. Genet.. 2016 Feb 1;25(3):497-513