Abstract
LIS1, a microtubule-associated protein, is required for neuronal migration, but the precise mechanism of LIS1 function is unknown. We identified a LIS1 interacting protein encoded by a mouse homolog of NUDE, a nuclear distribution gene in A. nidulans and a multicopy suppressor of the LIS1 homolog, NUDF. mNudE is located in the centrosome or microtubule organizing center (MTOC), and interacts with six different centrosomal proteins. Overexpression of mNudE dissociates gamma-tubulin from the centrosome and disrupts microtubule organization. Missense mutations that disrupt LIS1 function block LIS1-mNudE binding. Moreover, misexpression of the LIS1 binding domain of mNudE in Xenopus embryos disrupts the architecture and lamination of the CNS. Thus, LIS1-mNudE interactions may regulate neuronal migration through dynamic reorganization of the MTOC.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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1-Alkyl-2-acetylglycerophosphocholine Esterase
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Animals
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COS Cells
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Central Nervous System / embryology*
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Central Nervous System / metabolism*
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Centrosome / metabolism*
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Embryo, Nonmammalian / abnormalities
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Embryo, Nonmammalian / pathology
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Fungal Proteins / genetics
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Fungal Proteins / metabolism*
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Gene Expression Regulation, Developmental
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Mice
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Microtubule-Associated Proteins / genetics
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Microtubule-Associated Proteins / metabolism*
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Molecular Sequence Data
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Mutagenesis, Site-Directed
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Protein Binding / genetics
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Protein Structure, Tertiary / genetics
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RNA, Messenger / biosynthesis
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Sequence Homology, Amino Acid
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Substrate Specificity / physiology
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Tubulin / metabolism
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Two-Hybrid System Techniques
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Xenopus
Substances
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Fungal Proteins
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Microtubule-Associated Proteins
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RNA, Messenger
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RO-11 protein, Neurospora crassa
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Tubulin
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1-Alkyl-2-acetylglycerophosphocholine Esterase
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Pafah1b1 protein, mouse