The Drosophila fragile X mental retardation protein controls actin dynamics by directly regulating profilin in the brain.
Loss of Fragile X mental retardation protein (FMRP) function causes the highly prevalent Fragile X syndrome [1 and 2]. Identifying targets for the RNA binding FMRP is a major challenge and an important goal of research into the pathology of the disease. Perturbations in neuronal development and circadian behavior are seen in Drosophila dfmr1 mutants. Here we show that regulation of the actin cytoskeleton is under dFMRP control. dFMRP binds the mRNA of the Drosophila profilin homolog and negatively regulates Profilin protein expression. An increase in Profilin mimics the phenotype of dfmr1 mutants. Conversely, decreasing Profilin levels suppresses dfmr1 phenotypes. These data place a new emphasis on actin misregulation as a major problem in fmr1 mutant neurons.
Reeve
Simon P
SP
Laboratory of Neurogenetics, Department of Human Genetics, Flanders Interuniversity Institute for Biotechnology, University of Leuven School of Medicine, 3000 Leuven, Belgium.
Bassetto
Laura
L
Genova
Ginka K
GK
Kleyner
Yelena
Y
Leyssen
Maarten
M
Jackson
F Rob
FR
Hassan
Bassem A
BA
D000199:Actins / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000502:physiology*; D002478:Cells, Cultured; D003285:Contractile Proteins / Q000235:genetics* / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D051860:Fragile X Messenger Ribonucleoprotein 1; D005786:Gene Expression Regulation; D008840:Microfilament Proteins / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D051304:Profilins; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D013477:Superior Colliculi / Q000378:metabolism / Q000473:pathology; D020744:rac GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism
D000199:Actins; D003285:Contractile Proteins; D029721:Drosophila Proteins; D051860:Fragile X Messenger Ribonucleoprotein 1; D008840:Microfilament Proteins; D051304:Profilins; D016601:RNA-Binding Proteins; D020744:rac GTP-Binding Proteins; C467328:FMR1 protein, Drosophila; C090146:Rac1 protein, Drosophila