Fig. 1

Model for a postsynaptic FMRP signaling. At synapses, FMRP translational control is released upon TrkB tyrosin kinase signaling activated by BDNF (Napoli et al. 2008) and/or group I mGluRs cascade activated by DHPG (Napoli et al. 2008; Narayanan et al. 2007; Narayanan et al. 2008; Osterweil et al. 2010). Two alternative models have been proposed for the mGluR signaling upstream FMRP. The first one (A) proposes that the kinase ERK1/2 activation releases FMRP translational inhibition (Osterweil et al. 2010). The second one (B) implicates a bimodal PP2A/S6K signaling: an early dephosphorylation by PP2A (B.1) activates translation; sustained DHPG stimulation activates mTOR pathway (B.2), which suppresses PP2A activity and stimulates S6K, thus leading to FMRP phosphorylation and translational block (Narayanan et al. 2007; Narayanan et al. 2008). Furthermore, activation of group I mGluRs induces an early raise of FMRP due to protein synthesis (Antar et al. 2004; Ferrari et al. 2007; Kao et al. 2010) followed by a proteasome-dependent degradation of the protein (Hou et al. 2006; Zhao et al. 2011), restoring normal FMRP levels. Early events are indicated with black arrows, while late events induced by sustained stimulation are indicated by white arrows