Bicaudal-D regulates fragile X mental retardation protein levels, motility, and function during neuronal morphogenesis.
The expression of the RNA-binding factor Fragile X mental retardation protein (FMRP) is disrupted in the most common inherited form of cognitive deficiency in humans. FMRP controls neuronal morphogenesis by mediating the translational regulation and localization of a large number of mRNA targets, and these functions are closely associated with transport of FMRP complexes within neurites by microtubule-based motors. However, the mechanisms that link FMRP to motors and regulate its transport are poorly understood. Here we show that FMRP is complexed with Bicaudal-D (BicD) through a domain in the latter protein that mediates linkage of cargoes with the minus-end-directed motor dynein. We demonstrate in Drosophila that the motility and, surprisingly, levels of FMRP protein are dramatically reduced in BicD mutant neurons, leading to a paucity of FMRP within processes. We also provide functional evidence that BicD and FMRP cooperate to control dendritic morphogenesis in the larval nervous system. Our findings open new perspectives for understanding localized mRNA functions in neurons.
Bianco
Ambra
A
Cell Biology Division, MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH, UK.
Dienstbier
Martin
M
Salter
Hannah K
HK
Gatto
Graziana
G
Bullock
Simon L
SL
D000818:Animals; D001921:Brain / Q000196:embryology / Q000378:metabolism; D003712:Dendrites / Q000378:metabolism; D004330:Drosophila / Q000196:embryology / Q000378:metabolism*; D029721:Drosophila Proteins / Q000378:metabolism / Q000502:physiology*; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D007814:Larva / Q000378:metabolism; D009024:Morphogenesis; D055495:Neurogenesis; D009474:Neurons / Q000378:metabolism*; D021381:Protein Transport
D029721:Drosophila Proteins; D051860:Fragile X Messenger Ribonucleoprotein 1; C061998:BicD protein, Drosophila