EFA6A, an exchange factor for Arf6, regulates early steps in ciliogenesis

Author:

Partisani Mariagrazia1,Baron Carole L.1,Ghossoub Rania2,Fayad Racha1,Pagnotta Sophie3,Abélanet Sophie1,Macia Eric1,Brau Frédéric1,Lacas-Gervais Sandra3,Benmerah Alexandre4ORCID,Luton Frédéric1,Franco Michel1ORCID

Affiliation:

1. Institut de Pharmacologie Moléculaire et Cellulaire (IPMC), UMR 7275 CNRS-Université Côte d'Azur, 660, route des lucioles, 06560 Valbonne, France

2. Centre de Recherche en Cancérologie de Marseille (CRCM), Inserm, U1068-CNRS UMR7258, Aix-Marseille Université, Institut Paoli-Calmettes, 13009 Marseille, France

3. Centre Commun de Microscopie Appliquée (CCMA), Université Côte d'Azur Parc Valrose, 06103 Nice cedex 2, France

4. Université de Paris, Imagine Institute, Laboratory of Inherited Kidney Diseases, INSERM UMR 1163, F-75015, Paris, France

Abstract

ABSTRACT Ciliogenesis is a coordinated process initiated by the recruitment and fusion of pre-ciliary vesicles at the distal appendages of the mother centriole through mechanisms that remain unclear. Here, we report that EFA6A (also known as PSD), an exchange factor for the small G protein Arf6, is involved in early stage of ciliogenesis by promoting the fusion of distal appendage vesicles forming the ciliary vesicle. EFA6A is present in the vicinity of the mother centriole before primary cilium assembly and prior to the arrival of Arl13B-containing vesicles. During ciliogenesis, EFA6A initially accumulates at the mother centriole and later colocalizes with Arl13B along the ciliary membrane. EFA6A depletion leads to the inhibition of ciliogenesis, the absence of centrosomal Rab8-positive structures and the accumulation of Arl13B-positive vesicles around the distal appendages. Our results uncover a novel fusion machinery, comprising EFA6A, Arf6 and Arl13B, that controls the coordinated fusion of ciliary vesicles docked at the distal appendages of the mother centriole.

Funder

Centre National de la Recherche Scientifique

Association pour la Recherche contre le Cancer

Agence Nationale pour la Recherche

Publisher

The Company of Biologists

Subject

Cell Biology

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