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FMRP, the protein lacking in fragile X syndrome, works with three autism-linked proteins to fine-tune the connections between neurons, according to a study published 21 December in Cell1.
FMRP sometimes works with an autism-linked protein called MEF2 to regulate the expression of various genes.
By simply tweaking the levels of three other proteins, including the autism-linked proteins PCDH10 and PSD95, FMRP and MEF2 orchestrate a series of changes that ultimately influence learning, memory and other complex cognitive processes.
Specifically, they function together to prune neuronal junctions, or synapses, following neuronal activity. The new study shows that they do this by sending PSD95 — a scaffolding protein that sits at the receiving ends of neurons — to the cell’s clean-up crew for its disposal.
FMRP’s role in this pathway of destruction is to enable a protein called MDM2 to add a chemical tag, ubiquitin, to PSD95. Without FMRP, MDM2 is waylaid by another protein and doesn’t travel to the synapse.
MEF2 initiates expression of PCH10, which brings the ubiquitin-tagged PSD95 into contact with the proteasome, a large protein complex that breaks down proteins with this tag.
1: Tsai N.P. et al. Cell 151, 1581-1594 (2012) PubMed