The study of the determinants controlling Arpp19 phosphatase-inhibitory activity reveals an Arpp19/PP2A-B55 feedback loop

Jean Claude Labbé, Suzanne Vigneron, Francisca Méchali, Perle Robert, Sylvain Roque, Cindy Genoud, Perrine Goguet-Rubio, Phillipe Barthe, Gilles Labesse, Martin Cohen-Gonsaud, Anna Castro () and Thierry Lorca ()
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Jean Claude Labbé: Université de Montpellier, Centre de Recherche en Biologie Cellulaire de Montpellier (CRBM) CNRS, UMR 5237
Suzanne Vigneron: Université de Montpellier, Centre de Recherche en Biologie Cellulaire de Montpellier (CRBM) CNRS, UMR 5237
Francisca Méchali: Université de Montpellier, Centre de Recherche en Biologie Cellulaire de Montpellier (CRBM) CNRS, UMR 5237
Perle Robert: Université de Montpellier, Centre de Recherche en Biologie Cellulaire de Montpellier (CRBM) CNRS, UMR 5237
Sylvain Roque: Université de Montpellier, Centre de Recherche en Biologie Cellulaire de Montpellier (CRBM) CNRS, UMR 5237
Cindy Genoud: Université de Montpellier, Centre de Recherche en Biologie Cellulaire de Montpellier (CRBM) CNRS, UMR 5237
Perrine Goguet-Rubio: Université de Montpellier, Centre de Recherche en Biologie Cellulaire de Montpellier (CRBM) CNRS, UMR 5237
Phillipe Barthe: Université de Montpellier
Gilles Labesse: Université de Montpellier
Martin Cohen-Gonsaud: Université de Montpellier
Anna Castro: Université de Montpellier, Centre de Recherche en Biologie Cellulaire de Montpellier (CRBM) CNRS, UMR 5237
Thierry Lorca: Université de Montpellier, Centre de Recherche en Biologie Cellulaire de Montpellier (CRBM) CNRS, UMR 5237

Nature Communications, 2021, vol. 12, issue 1, 1-19

Abstract: Abstract Arpp19 is a potent PP2A-B55 inhibitor that regulates this phosphatase to ensure the stable phosphorylation of mitotic/meiotic substrates. At G2-M, Arpp19 is phosphorylated by the Greatwall kinase on S67. This phosphorylated Arpp19 form displays a high affinity to PP2A-B55 and a slow dephosphorylation rate, acting as a competitor of PP2A-B55 substrates. The molecular determinants conferring slow dephosphorylation kinetics to S67 are unknown. PKA also phosphorylates Arpp19. This phosphorylation performed on S109 is essential to maintain prophase I-arrest in Xenopus oocytes although the underlying signalling mechanism is elusive. Here, we characterize the molecular determinants conferring high affinity and slow dephosphorylation to S67 and controlling PP2A-B55 inhibitory activity of Arpp19. Moreover, we show that phospho-S109 restricts S67 phosphorylation by increasing its catalysis by PP2A-B55. Finally, we discover a double feed-back loop between these two phospho-sites essential to coordinate the temporal pattern of Arpp19-dependent PP2A-B55 inhibition and Cyclin B/Cdk1 activation during cell division.

Date: 2021
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-23657-0

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DOI: 10.1038/s41467-021-23657-0

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