Human Molecular Genetics Advance Access first published online on September 19, 2007
This version published online on September 21, 2007
Human Molecular Genetics, doi:10.1093/hmg/ddm263
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The Fragile X Mental Retardation Protein is a molecular adaptor between the neurospecific KIF3C kinesin and dendritic RNA granules
1 Unité de Recherche en Génétique Humaine et Moléculaire, Centre de recherche Hôpital Saint-François d'Assise, le CHUQ, Québec, G1L 3L5, Canada 2 Département de Biologie Médicale, Faculté de Médecine, Université Laval, Québec, Canada 3 Génétique et Biologie Moléculaire du Retard Mental, CNRS UMR6543, Faculté de Médecine, Université de Nice Sophia-Antipolis, 06107, NICE-France 4 INSERM U675, IFR2, Faculté de Médecine Xavier Bichat, Université Paris VII, 75018 Paris, France
Corresponding author : Edouard W. Khandjian, URGHM, Centre de recherche Hôpital St François d'Assise 10 rue de l'Espinay, Québec G1L 3L5, PQ, Canada. Tel: +1 418 525 4402 Fax: +1 418 525 4195 Email: edward.khandjian{at}crsfa.ulaval.ca
Received May 25, 2007; Revised August 15, 2007; Accepted September 11, 2007
Fragile X Mental Retardation 1 protein (FMRP) is an RNA-binding protein whose absence results in the Fragile X Syndrome, the most common inherited form of mental retardation. FMRP contains multiple domains with apparently differential affinity to mRNA and interacts also with protein partners present in ribonucleoprotein complexes called RNA granules. In neurons, these particles travel along dendrites and axons to translocate mRNAs to specific destinations in spines and growth cones, where local synthesis of neuro-specific proteins is taking place. However the molecular mechanisms of how RNA granules are translocated to dendrites remained unknown. We report here the identification and characterization of the motor protein KIF3C as a novel FMRP-interacting protein. In addition, using time-lapse videomicroscopy, we studied the dynamics and kinetics of FMRP-containing RNA granules in dendrites and show that a KIF3C dominant-negative impedes their distal transport. We therefore propose that, in addition to modulate the translation of its mRNA targets, FMRP acts also as a molecular adaptor between RNA granules and the neurospecific kinesin KIF3C that powers their transport along neuronal microtubules.
* Present address: INSERM U567-CNRS UMR8104, Institut Cochin, Université René Descartes-Paris V, 75014 Paris, France
This title page of this paper was versioned to add a co-author, Sandra Tremblay, and the present address of Xavier Jaglin. on page 34, we have kept the figures a) and b) and have adjusted the legend so the legend refers to the correct figure part.
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