Human Molecular Genetics Advance Access originally published online on September 19, 2007
Human Molecular Genetics 2007 16(24):3047-3058; 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, Canada G1L 3L5, 2 Département de Biologie Médicale, Faculté de Médecine, Université Laval, Québec, Canada, 3 CNRS UMR6543, Faculté de Médecine, Université de Nice Sophia-Antipolis, 06 107, NICE-France, 4 INSERM U675, IFR2, Faculté de Médecine Xavier Bichat, Université Paris VII, 75 018 Paris, France
* To whom correspondence should be addressed at: URGHM, Centre de recherche Hôpital St François d’Assise, 10 rue de l’Espinay, Québec, PQ, Canada G1L 3L5. Tel: +1 4185254402; Fax: +1 4185254195; 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
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