title: Mutations in cytoplasmic dynein and its regulators cause malformations of cortical development and neurodegenerative diseases.
abstract: Neurons are highly specialized for the processing and transmission of electrical signals and use cytoskeleton-based motor proteins to transport different vesicles and cellular materials. Abnormalities in intracellular transport are thought to be a critical factor in the degeneration and death of neurons in both the central and peripheral nervous systems. Several recent studies describe disruptive mutations in the minus-end-directed microtubule motor cytoplasmic dynein that are directly linked to human motor neuropathies, such as SMA (spinal muscular atrophy) and axonal CMT (Charcot-Marie-Tooth) disease or malformations of cortical development, including lissencephaly, pachygyria and polymicrogyria. In addition, genetic defects associated with these and other neurological disorders have been found in multifunctional adaptors that regulate dynein function, including the dynactin subunit p150(Glued), BICD2 (Bicaudal D2), Lis-1 (lissencephaly 1) and NDE1 (nuclear distribution protein E). In the present paper we provide an overview of the disease-causing mutations in dynein motors and regulatory proteins that lead to a broad phenotypic spectrum extending from peripheral neuropathies to cerebral malformations.
authors.affiliation: *Division of Cell Biology, Department of Biology, Faculty of Science, Utrecht University, 3584 CH Utrecht, The Netherlands.
authors.forename: Joanna
authors.initials: J
authors.lastname: Lipka
authors.forename: Marijn
authors.initials: M
authors.lastname: Kuijpers
authors.forename: Jacek
authors.initials: J
authors.lastname: Jaworski
authors.forename: Casper C
authors.initials: CC
authors.lastname: Hoogenraad
mesh_terms: D000818:Animals; D056445:Cytoplasmic Dyneins / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D054220:Malformations of Cortical Development / Q000201:enzymology* / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D019636:Neurodegenerative Diseases / Q000201:enzymology* / Q000235:genetics* / Q000378:metabolism
chemical_list: D056445:Cytoplasmic Dyneins