Protein-protein interactions, cytoskeletal regulation and neuronal migration.
Neuronal migration, like the migration of many cell types, requires an extensive rearrangement of cell shape, mediated by changes in the cytoskeleton. The genetic analysis of human brain malformations has identified several biochemical players in this process, including doublecortin (DCX) and LIS1, mutations of which cause a profound migratory disturbance known as lissencephaly ('smooth brain') in humans. Studies in mice have identified additional molecules such as Cdk5, P35, Reelin, Disabled and members of the LDL superfamily of receptors. Understanding the cell biology of these molecules has been a challenge, and it is not known whether they function in related biochemical pathways or in very distinct processes. The last year has seen rapid advances in the biochemical analysis of several such molecules. This analysis has revealed roles for some of these molecules in cytoskeletal regulation and has shown an unexpected conservation of the genetic pathways that regulate neuronal migration in humans and nuclear movement in simple eukaryotic organisms.
Feng
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Y
Department of Neurology, Harvard Medical School, Beth Israel Deaconess Medical Centre, Harvard Institutes of Medicine, 4 Blackfan Circle, Boston, Massachusetts 02115, USA.
Walsh
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CA
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D000818:Animals; D001921:Brain / Q000002:abnormalities / Q000378:metabolism / Q000503:physiopathology; D002465:Cell Movement / Q000235:genetics*; D048429:Cell Size / Q000235:genetics*; D003598:Cytoskeletal Proteins / Q000235:genetics* / Q000378:metabolism; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D009421:Nervous System Malformations / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism; D000091042:Reelin Protein
D003598:Cytoskeletal Proteins; C000714328:DCX protein, human; C000714847:Dcx protein, mouse; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D000091042:Reelin Protein; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; C084102:PAFAH1B1 protein, human; C000717127:RELN protein, human; C000717128:Reln protein, mouse