Rho proteins, mental retardation and the cellular basis of cognition.
For several decades, it has been known that mental retardation (MR) is associated with abnormalities in dendrites and dendritic spines. The recent cloning of seven genes that cause nonspecific MR when mutated provides important insights in the cellular mechanisms that result in the dendritic abnormalities associated with MR. Three of the encoded proteins, oligophrenin 1, PAK3 and alpha PIX, interact directly with Rho GTPases. Rho GTPases are key signaling proteins that integrate extracellular and intracellular signals to orchestrate coordinated changes in the actin cytoskeleton essential for directed neurite outgrowth and the regulation of synaptic connectivity. Although many details of the cell biology of Rho signaling in the CNS are still unclear, a picture is unfolding showing how mutations that alter Rho signaling result in abnormal neuronal connectivity and deficient cognitive functioning in humans. Conversely, these findings illuminate the cellular mechanisms underlying normal cognitive function.
Ramakers
Ger J A
GJ
Neurons and Networks, Netherlands Institute for Brain Research, Graduate School Neurosciences Amsterdam, Meibergdreef 33, 1105 AZ Amsterdam ZO, The Netherlands.
D000199:Actins / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000002:abnormalities* / Q000201:enzymology / Q000473:pathology; D002454:Cell Differentiation / Q000235:genetics*; D003071:Cognition / Q000502:physiology; D003712:Dendrites / Q000201:enzymology / Q000473:pathology*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D006801:Humans; D008607:Intellectual Disability / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D009421:Nervous System Malformations / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D009434:Neural Pathways / Q000002:abnormalities / Q000201:enzymology / Q000473:pathology; D020741:rho GTP-Binding Proteins / Q000235:genetics* / Q000378:metabolism
D000199:Actins; D020741:rho GTP-Binding Proteins