The translation regulatory subunit eIF3f controls the kinase-dependent mTOR signaling required for muscle differentiation and hypertrophy in mouse

Alfredo Csibi (1) , Karen Cornille (1) , Marie-Pierre Leibovitch (1) , Anne Poupon (2) , Lionel Tintignac (1) , Anthony Sanchez (1) , Serge Leibovitch (1)

1 DCC - Différenciation Cellulaire et Croissance
2 PRC - Physiologie de la reproduction et des comportements [Nouzilly]

The mTORC1 pathway is required for both the terminal muscle differentiation and hypertrophy by controlling the mammalian translational machinery via phosphorylation of S6K1 and 4E-BP1. mTOR and S6K1 are connected by interacting with the eIF3 initiation complex. The regulatory subunit eIF3f plays a major role in muscle hypertrophy and is a key target that accounts for MAFbx function during atrophy. Here we present evidence that in MAFbx-induced atrophy the degradation of eIF3f suppresses S6K1 activation by mTOR, whereas an eIF3f mutant insensitive to MAFbx polyubiquitination maintained persistent phosphorylation of S6K1 and rpS6. During terminal muscle differentiation a conserved TOS motif in eIF3f connects mTOR/raptor complex, which phosphorylates S6K1 and regulates downstream effectors of mTOR and Cap-dependent translation initiation. Thus eIF3f plays a major role for proper activity of mTORC1 to regulate skeletal muscle size.

Mots clés: mammifères

Domaines: Biologie animale

Alfredo Csibi, Karen Cornille, Marie-Pierre Leibovitch, Anne Poupon, Lionel Tintignac, et al.. The translation regulatory subunit eIF3f controls the kinase-dependent mTOR signaling required for muscle differentiation and hypertrophy in mouse. PLoS ONE, 2010, 5 (2), pp.e8994. ⟨10.1371/journal.pone.0008994⟩. ⟨hal-01129600⟩