PT - JOURNAL ARTICLE AU - Abekhoukh, Sabiha AU - Sahin, H. Bahar AU - Grossi, Mauro AU - Zongaro, Samantha AU - Maurin, Thomas AU - Madrigal, Irene AU - Kazue-Sugioka, Daniele AU - Raas-Rothschild, Annick AU - Doulazmi, Mohamed AU - Carrera, Pilar AU - Stachon, Andrea AU - Scherer, Steven AU - Drula Do Nascimento, Maria Rita AU - Trembleau, Alain AU - Arroyo, Ignacio AU - Szatmari, Peter AU - Smith, Isabel M. AU - Milà, Montserrat AU - Smith, Adam C. AU - Giangrande, Angela AU - Caillé, Isabelle AU - Bardoni, Barbara TI - New insights into the regulatory function of CYFIP1 in the context of WAVE- and FMRP-containing complexes AID - 10.1242/dmm.025809 DP - 2017 Apr 01 TA - Disease Models & Mechanisms PG - 463--474 VI - 10 IP - 4 4099 - http://dmm.biologists.org/content/10/4/463.short 4100 - http://dmm.biologists.org/content/10/4/463.full SO - Dis Models Mech2017 Apr 01; 10 AB - Cytoplasmic FMRP interacting protein 1 (CYFIP1) is a candidate gene for intellectual disability (ID), autism, schizophrenia and epilepsy. It is a member of a family of proteins that is highly conserved during evolution, sharing high homology with its Drosophila homolog, dCYFIP. CYFIP1 interacts with the Fragile X mental retardation protein (FMRP, encoded by the FMR1 gene), whose absence causes Fragile X syndrome, and with the translation initiation factor eIF4E. It is a member of the WAVE regulatory complex (WRC), thus representing a link between translational regulation and the actin cytoskeleton. Here, we present data showing a correlation between mRNA levels of CYFIP1 and other members of the WRC. This suggests a tight regulation of the levels of the WRC members, not only by post-translational mechanisms, as previously hypothesized. Moreover, we studied the impact of loss of function of both CYFIP1 and FMRP on neuronal growth and differentiation in two animal models – fly and mouse. We show that these two proteins antagonize each other's function not only during neuromuscular junction growth in the fly but also during new neuronal differentiation in the olfactory bulb of adult mice. Mechanistically, FMRP and CYFIP1 modulate mTor signaling in an antagonistic manner, likely via independent pathways, supporting the results obtained in mouse as well as in fly at the morphological level. Collectively, our results illustrate a new model to explain the cellular roles of FMRP and CYFIP1 and the molecular significance of their interaction.