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Research Article
EFA6A, an exchange factor for Arf6, regulates early steps in ciliogenesis
Mariagrazia Partisani, Carole L. Baron, Rania Ghossoub, Racha Fayad, Sophie Pagnotta, Sophie Abélanet, Eric Macia, Frédéric Brau, Sandra Lacas-Gervais, Alexandre Benmerah, Frédéric Luton, Michel Franco
Journal of Cell Science 2021 134: jcs249565 doi: 10.1242/jcs.249565 Published 22 January 2021
Mariagrazia Partisani
1Institut de Pharmacologie Moléculaire et Cellulaire (IPMC), UMR 7275 CNRS-Université Côte d'Azur, 660, route des lucioles, 06560 Valbonne, France
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Carole L. Baron
1Institut de Pharmacologie Moléculaire et Cellulaire (IPMC), UMR 7275 CNRS-Université Côte d'Azur, 660, route des lucioles, 06560 Valbonne, France
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Rania Ghossoub
2Centre de Recherche en Cancérologie de Marseille (CRCM), Inserm, U1068-CNRS UMR7258, Aix-Marseille Université, Institut Paoli-Calmettes, 13009 Marseille, France
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Racha Fayad
1Institut de Pharmacologie Moléculaire et Cellulaire (IPMC), UMR 7275 CNRS-Université Côte d'Azur, 660, route des lucioles, 06560 Valbonne, France
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Sophie Pagnotta
3Centre Commun de Microscopie Appliquée (CCMA), Université Côte d'Azur Parc Valrose, 06103 Nice cedex 2, France
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Sophie Abélanet
1Institut de Pharmacologie Moléculaire et Cellulaire (IPMC), UMR 7275 CNRS-Université Côte d'Azur, 660, route des lucioles, 06560 Valbonne, France
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Eric Macia
1Institut de Pharmacologie Moléculaire et Cellulaire (IPMC), UMR 7275 CNRS-Université Côte d'Azur, 660, route des lucioles, 06560 Valbonne, France
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Frédéric Brau
1Institut de Pharmacologie Moléculaire et Cellulaire (IPMC), UMR 7275 CNRS-Université Côte d'Azur, 660, route des lucioles, 06560 Valbonne, France
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Sandra Lacas-Gervais
3Centre Commun de Microscopie Appliquée (CCMA), Université Côte d'Azur Parc Valrose, 06103 Nice cedex 2, France
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Alexandre Benmerah
4Université de Paris, Imagine Institute, Laboratory of Inherited Kidney Diseases, INSERM UMR 1163, F-75015, Paris, France
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  • ORCID record for Alexandre Benmerah
Frédéric Luton
1Institut de Pharmacologie Moléculaire et Cellulaire (IPMC), UMR 7275 CNRS-Université Côte d'Azur, 660, route des lucioles, 06560 Valbonne, France
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Michel Franco
1Institut de Pharmacologie Moléculaire et Cellulaire (IPMC), UMR 7275 CNRS-Université Côte d'Azur, 660, route des lucioles, 06560 Valbonne, France
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  • For correspondence: franco@ipmc.cnrs.fr

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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.

Footnotes

  • Competing interests

    The authors declare no competing or financial interests.

  • Author contributions

    Conceptualization: R.G., A.B., F.L., M.F.; Methodology: S.A., E.M., F.B.; Software: S.A., F.B.; Validation: M.P., C.L.B., R.F., S.P., S.L.-G., M.F.; Formal analysis: E.M.; Investigation: M.P., C.L.B., R.G., R.F., S.P., E.M., S.L.-G., M.F.; Resources: M.P., C.L.B., R.F.; Data curation: S.A.; Writing - original draft: A.B., F.L., M.F.; Writing - review & editing: M.F.; Supervision: S.L.-G., F.L.; M.F.; Project administration: M.F.; Funding acquisition: F.L., M.F.

  • Funding

    This work is supported by the Centre National de la Recherche Scientifique, the Association pour la Recherche contre le Cancer and the Agence Nationale pour la Recherche (ANR) through the Investissement pour le Futur Labex Signalife Program ref ANR-11Labx-0028-01. This work is also supported by State funding from the ANR under the ‘Investissements d'avenir’ program (ANR-10-IAHU-01).

  • Supplementary information

    Supplementary information available online at https://jcs.biologists.org/lookup/doi/10.1242/jcs.249565.supplemental

  • Received May 28, 2020.
  • Accepted November 20, 2020.
  • © 2021. Published by The Company of Biologists Ltd
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Keywords

  • Arf6
  • Rab8
  • Arl13B
  • DAVs fusion
  • EFA6A
  • Ciliogenesis
  • Membrane trafficking

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Research Article
EFA6A, an exchange factor for Arf6, regulates early steps in ciliogenesis
Mariagrazia Partisani, Carole L. Baron, Rania Ghossoub, Racha Fayad, Sophie Pagnotta, Sophie Abélanet, Eric Macia, Frédéric Brau, Sandra Lacas-Gervais, Alexandre Benmerah, Frédéric Luton, Michel Franco
Journal of Cell Science 2021 134: jcs249565 doi: 10.1242/jcs.249565 Published 22 January 2021
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Research Article
EFA6A, an exchange factor for Arf6, regulates early steps in ciliogenesis
Mariagrazia Partisani, Carole L. Baron, Rania Ghossoub, Racha Fayad, Sophie Pagnotta, Sophie Abélanet, Eric Macia, Frédéric Brau, Sandra Lacas-Gervais, Alexandre Benmerah, Frédéric Luton, Michel Franco
Journal of Cell Science 2021 134: jcs249565 doi: 10.1242/jcs.249565 Published 22 January 2021

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