Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

Of 11 genes involved in nonspecific X-linked mental retardation (MRX), three encode regulators or effectors of the Rho GTPases, suggesting an important role for Rho signaling in cognitive function. It remains unknown, however, how mutations in Rho-linked genes lead to MRX. Here we report that oligophrenin-1, a Rho-GTPase activating protein that is absent in a family affected with MRX, is required for dendritic spine morphogenesis. Using RNA interference and antisense RNA approaches, we show that knock-down of oligophrenin-1 levels in CA1 neurons in rat hippocampal slices significantly decreases spine length. This phenotype can be recapitulated using an activated form of RhoA and rescued by inhibiting Rho-kinase, indicating that reduced oligophrenin-1 levels affect spine length by increasing RhoA and Rho-kinase activities. We further demonstrate an interaction between oligophrenin-1 and the postsynaptic adaptor protein Homer. Our findings provide the first insight into how mutations in a Rho-linked MRX gene may compromise neuronal function.

Original publication

DOI

10.1038/nn1210

Type

Journal article

Journal

Nat Neurosci

Publication Date

04/2004

Volume

7

Pages

364 - 372

Keywords

Animals, Cell Size, Cytoskeletal Proteins, Dendrites, Down-Regulation, GTPase-Activating Proteins, Hippocampus, Mental Retardation, X-Linked, Mice, Morphogenesis, Neurites, Neurons, Nuclear Proteins, Organ Culture Techniques, RNA Interference, RNA, Antisense, Rats, Synapses, Transfection