Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.6.4.4 (
kinesin
)
5,033
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
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.
...
PMID:The fragile X mental retardation protein is a molecular adaptor between the neurospecific KIF3C kinesin and dendritic RNA granules. 1788 55
The function of local protein synthesis in synaptic plasticity and its dysregulation in fragile X syndrome (FXS) is well studied, however the contribution of regulated mRNA transport to this function remains unclear. We report a function for the
fragile X mental retardation protein
(
FMRP
) in the rapid, activity-regulated transport of mRNAs important for synaptogenesis and plasticity. mRNAs were deficient in glutamatergic signaling-induced dendritic localization in neurons from Fmr1 KO mice, and single mRNA particle dynamics in live neurons revealed diminished kinesis. Motor-dependent translocation of
FMRP
and cognate mRNAs involved the C terminus of
FMRP
and kinesin light chain, and KO brain showed reduced
kinesin
-associated mRNAs. Acute suppression of
FMRP
and target mRNA transport in WT neurons resulted in altered filopodia-spine morphology that mimicked the FXS phenotype. These findings highlight a mechanism for stimulus-induced dendritic mRNA transport and link its impairment in a mouse model of FXS to altered developmental morphologic plasticity.
...
PMID:A direct role for FMRP in activity-dependent dendritic mRNA transport links filopodial-spine morphogenesis to fragile X syndrome. 1853 20
