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.