The PRKAA1/AMPKα1 pathway triggers autophagy during CSF1-induced human monocyte differentiation and is a potential target in CMML

Sandrine Obba, Zoheir Hizir, Laurent Boyer, Dorothée Selimoglu-Buet, Anja Pfeifer, Gregory Michel, Mohamed Amine Hamouda, Diogo Gonçalvés, Michael Cerezo, Sandrine Marchetti, Stephane Rocchi, Nathalie Droin, Thomas Cluzeau, Guillaume Robert, Frederic Luciano, Bernard Robaye, Marc Foretz, Benoit Viollet, Laurence Legros, Eric SolaryPatrick Auberger, Arnaud Jacquel

    Résultats de recherche: Contribution à un journalArticleRevue par des pairs

    87 Citations (Scopus)

    Résumé

    Autophagy is induced during differentiation of human monocytes into macrophages that is mediated by CSF1/CSF- 1/M-CSF (colony stimulating factor 1 [macrophage]). However, little is known about the molecular mechanisms that link CSF1 receptor engagement to the induction of autophagy. Here we show that the CAMKK2-PRKAA1-ULK1 pathway is required for CSF1-induced autophagy and human monocyte differentiation. We reveal that this pathway links P2RY6 to the induction of autophagy, and we decipher the signaling network that links the CSF1 receptor to P2RY6-mediated autophagy and monocyte differentiation. In addition, we show that the physiological P2RY6 ligand UDP and the specific P2RY6 agonist MRS2693 can restore normal monocyte differentiation through reinduction of autophagy in primary myeloid cells from some but not all chronic myelomonocytic leukemia (CMML) patients. Collectively, our findings highlight an essential role for PRKAA1-mediated autophagy during differentiation of human monocytes and pave the way for future therapeutic interventions for CMML.

    langue originaleAnglais
    Pages (de - à)1114-1129
    Nombre de pages16
    journalAutophagy
    Volume11
    Numéro de publication7
    Les DOIs
    étatPublié - 1 janv. 2015

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