Proteins and the Fragile X pathway

Researchers at Yale School of Medicine in the US have identified a new regulatory target for the Fragile X mental retardation protein (FMRP).

The findings, published in the early online edition of the June Proceedings of the National Academy of Sciences, also have implications for autism, which shares a common physiological pathway with FXS.

Fragile X syndrome is mainly caused by a mutation in the FMR1 gene on the X chromosome, leading to the loss of FMRP, which is abundantly expressed in the brain and testes.

Without this protein, brain development is hampered and nerve cells cannot communicate with each other appropriately, resulting in the reduced ability to learn and memorise.

Fragile X syndrome affects about one in 4,000 males and one in 8,000 females. About 20 per cent of children with FXS have autism and about five percent of autistic children have FXS.

The research team led by Assistant Professor Yingqun Huang, from Yale's department of obstetrics and gynaecology, previously found that FMRP interacts with a nuclear mRNA export protein, NXF2, in the mouse brain and testes. In this study, the team used mouse neuronal cells to explore the functional characteristics of this interaction.

"We found that FMRP, together with NXF2, acts to down-regulate the expression of its target, the messenger RNA that encodes NXF1, which is an essential protein needed to transport most mRNAs from the nucleus to the cytoplasm of cells," Huang said.

"Our findings explain why the NXF1 protein level is much lower in the hippocampal neurons involved in learning and memory than in many other cells. This may suggest that a high level of NXF1 might hinder the function of these cells."

She said future studies will look more closely at how FMRP works with NXF2 to regulate its targets.

"We expect to identify more targets which are regulated by FMRP and NXF2. This will be a new direction in the FMRP research field."

Source: Yale University