title: Rho GTPase signaling at the synapse: implications for intellectual disability.
abstract: Intellectual disability (ID) imposes a major medical and social-economical problem in our society. It is defined as a global reduction in cognitive and intellectual abilities, associated with impaired social adaptation. The causes of ID are extremely heterogeneous and include non-genetic and genetic changes. Great progress has been made over recent years towards the identification of ID-related genes, resulting in a list of approximately 450 genes. A prominent neuropathological feature of patients with ID is altered dendritic spine morphogenesis. These structural abnormalities, in part, reflect impaired cytoskeleton remodeling and are associated with synaptic dysfunction. The dynamic, actin-rich nature of dendritic spines points to the Rho GTPase family as a central contributor, since they are key regulators of actin dynamics and organization. It is therefore not surprising that mutations in genes encoding regulators and effectors of the Rho GTPases have been associated with ID. This review will focus on the role of Rho GTPase signaling in synaptic structure/function and ID.
authors.affiliation: Donders Institute for Brain Cognition and Behavior, Radboud University Nijmegen Medical Center, Department Cognitive Neuroscience, the Netherlands.
authors.forename: Wei
authors.initials: W
authors.lastname: Ba
authors.forename: Jori
authors.initials: J
authors.lastname: van der Raadt
authors.forename: Nael
authors.initials: N
authors.lastname: Nadif Kasri
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism; D003599:Cytoskeleton / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D049229:Dendritic Spines / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D020690:GTPase-Activating Proteins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D055495:Neurogenesis / Q000235:genetics; D009473:Neuronal Plasticity; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D064067:Rho Guanine Nucleotide Exchange Factors; D015398:Signal Transduction; D013569:Synapses / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D054462:p21-Activated Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: C577410:ARHGEF9 protein, human; D000199:Actins; D003598:Cytoskeletal Proteins; D020690:GTPase-Activating Proteins; D020662:Guanine Nucleotide Exchange Factors; D009687:Nuclear Proteins; C111952:OPHN1 protein, human; D064067:Rho Guanine Nucleotide Exchange Factors; C465659:SRGAP3 protein, human; C515911:PAK3 protein, human; D054462:p21-Activated Kinases
keywords: Intellectual disability; Rho GTPase; Synapse; Synaptic plasticity