The X-linked mental retardation protein oligophrenin-1 is required for dendritic spine morphogenesis

Govek, E. E., Newey, S. E., Akerman, C. J., Cross, J. R., Van der Veken, L., Van Aelst, L. (April 2004) The X-linked mental retardation protein oligophrenin-1 is required for dendritic spine morphogenesis. Nat Neurosci, 7 (4). pp. 364-72. ISSN 1097-6256 (Print)

URL: https://www.ncbi.nlm.nih.gov/pubmed/15034583
DOI: 10.1038/nn1210

Abstract

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.

Item Type: Paper
Uncontrolled Keywords: Animals Cell Size physiology Cytoskeletal Proteins deficiency genetics metabolism Dendrites metabolism Down-Regulation GTPase-Activating Proteins deficiency genetics metabolism Hippocampus/cytology growth & development metabolism Mental Retardation, X-Linked genetics metabolism Mice Morphogenesis Neurites metabolism Neurons cytology metabolism Nuclear Proteins deficiency genetics metabolism Organ Culture Techniques RNA Interference physiology RNA, Antisense physiology Rats Synapses metabolism Transfection
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > GTPase
diseases & disorders > congenital hereditary genetic diseases > mental retardation
CSHL Authors:
Communities: CSHL labs > Van Aelst lab
Depositing User: CSHL Librarian
Date: April 2004
Date Deposited: 03 Feb 2012 17:42
Last Modified: 22 Feb 2017 21:53
Related URLs:
URI: http://repository.cshl.edu/id/eprint/22376

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