Rho-Linked Mental Retardation Genes

Chapter
Part of the Advances in Neurobiology book series (NEUROBIOL, volume 1)

Abstract

Mental retardation (MR) is generally defined as a global reduction in cognitive abilities, which manifests before the age of 18. The causes of MR are extremely heterogeneous, including environmental factors as well as genetic changes, such as chromosomal abnormalities and single-gene mutations. Great progress has been made in recent years towards the identification of MR genes, particularly X-linked MR genes. A largely remaining challenge, however, is to connect the genetic causes of MR to processes that establish and/or modify neuronal circuit function. Several of the currently identified genes are associated with MR code for regulators and effectors of the Rho subfamily of GTP-binding proteins, which are key regulators of the actin cytoskeleton. The identification and characterization of Rho-linked genes associated with different forms of MR have shed light on our current understanding as to how defective cellular signaling can result in abnormal neuronal connectivity, which can give rise to impaired information processing underlying cognitive function. Aberrations in defined Rho-mediated signaling pathways have been linked to defects in the formation and remodeling of dendritic spines and/or the maturation and activity-dependent modification of the efficacy of synapses. In this review, we focus on the role of Rho GTPases and their associated signaling molecules in the control of spine structure and synaptic function, and highlight their involvement in MR resulting from a variety of genetic mutations within regulators and effectors of these molecules.

Keywords

Mental retardation (MR) Dentritic spines Synaptic structure and function Actin cytoskeleton Rho GTPases Rho-linked MR genes Nonsyndromic and syndromic X-linked MR Autosomal syndromic MR 

Notes

Acknowledgments

Because of space limitations, we are not able to cite the work of many of our colleagues who have made valuable contributions to this field. LVA is supported by NSF and NIH grants. NNK is a postdoctoral fellow from the Fund for Scientific Research Flanders and is supported by the Human Frontiers Science Program.

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© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Department of NeurologySUNY Downstate Medical CenterBrooklynUSA
  2. 2.Cold Spring Harbor LaboratoryCold Spring HarborNew YorkUSA

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