Étude de la compartimentalisation de sous-populations de la Fragile X Mental Retardation Protein au sein de la cellule

Authors: Dury, Alain
Advisor: Khandjian, Edward WilliamDe Koninck, Paul
Abstract: Fragile X syndrome, a monogenic disease linked to the chromosome X, is the first cause of inherited mental retardation. The syndrome affects about one out of 4000 man, and one out of 6000 woman. Fragile X is caused by the inactivation of the Fragile X Mental retardation (FMR1) gene, leading to the absence of its product, the Fragile X Mental Retardation Protein (FMRP). The absence of FMRP, an RNA binding protein, is believed to cause translation dysregulation and defects in mRNA transport essential for local protein synthesis and for synaptic development and maturation. It is accepted that FMRP possesses a nuclear localisation signal (NLS), and a nuclear export signal (NES), allowing the protein to enter the nucleus, and possibly to exit from it as well. However, available antibodies do not allow to study the nuclear localisation of FMRP. Thanks to a new generation of monospecific antibodies developed in our laboratory, we were able to study the cytoplasmic and the nuclear distribution of FMRP. I will therefore shortly develop the fate of cytoplasmic FMRP (cFMRP) in neurons, and I will characterise the nuclear FMRP (nFMRP) that has been sought after for many years. nFMRP consists in particular nuclear FMRP isoforms that localize to Cajal bodies, structures described more than a century ago by the famous neuroscientist Santiago Ramon y Cajal. Data presented here also raise doubts on the nucleocytoplasmic traficking model, which relies on very few evidence. The discovery of nFMRP could have great implication in the Fragile X domain, opening a whole new field of investigation on the role of FMRP in the cell nucleus, and therefore on the consequences of its absence in patients.
Document Type: Thèse de doctorat
Issue Date: 2017
Open Access Date: 24 April 2018
Permalink: http://hdl.handle.net/20.500.11794/27704
Grantor: Université Laval
Collection:Thèses et mémoires

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