Research ArticleNeuroscience

Augmented noncanonical BMP type II receptor signaling mediates the synaptic abnormality of fragile X syndrome

See allHide authors and affiliations

Science Signaling  07 Jun 2016:
Vol. 9, Issue 431, pp. ra58
DOI: 10.1126/scisignal.aaf6060

BMP signaling underlies fragile X syndrome

Fragile X syndrome (FXS) is a heritable cognitive disability and autism spectrum disorder caused by loss of expression of the gene encoding the RNA binding protein FMRP. FMRP suppresses the translation of various mRNAs. Kashima et al. found that the transcript encoding the bone morphogenetic protein type II receptor (BMPR2) was a critical FMRP target that contributed to the neuronal morphology seen in FXS. Loss of FMRP in fruitfly and mice increased the abundance of BMPR2 and activated a downstream kinase LIMK1 in neurons; increased BMPR2 abundance and cofilin phosphorylation (suggesting increased LIMK1 activity) were also detected in postmortem brain tissue from FXS patients. Reducing signaling through the BMPR2-LIMK1 pathway suppressed abnormal dendritic spine growth in FXS model mice, suggesting that this might be a therapeutic option for FXS patients.

View Full Text

Stay Connected to Science Signaling