Research ArticleFRAGILE X SYNDROME

Neuronal activity drives FMRP- and HSPG-dependent matrix metalloproteinase function required for rapid synaptogenesis

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Sci. Signal.  07 Nov 2017:
Vol. 10, Issue 504, eaan3181
DOI: 10.1126/scisignal.aan3181

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Restraining MMPs or surface glypicans may treat FXS

The breakdown of the extracellular matrix, such as by matrix metalloproteinases (MMPs), helps cells to make protrusions and migrate. In neurons, this activity facilitates the growth and development of boutons that enable synaptogenesis, neuronal adaptability, and memory formation. MMP function is abnormally increased in patients with the intellectual disorder fragile X syndrome (FXS), whose neurons exhibit synaptic dysfunction and increased numbers of immature dendritic spines. In the FXS fly model, the abundance of the heparan sulfate proteoglycan receptor Dlp is also increased. Using flies, Dear et al. found that Dlp directly interacted with and recruited MMP1 to the neuronal cell surface, facilitating its secretion and activity underlying FXS-associated neurological phenotypes. Homologs of both exist in humans, suggesting a potential avenue for therapeutic development.