LIS1 regulates CNS lamination by interacting with mNudE, a central component of the centrosome.
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.
Feng
Y
Y
Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Institutes of Medicine, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.
Olson
E C
EC
Stukenberg
P T
PT
Flanagan
L A
LA
Kirschner
M W
MW
Walsh
C A
CA
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D000818:Animals; D019556:COS Cells; D002490:Central Nervous System / Q000196:embryology* / Q000378:metabolism*; D018385:Centrosome / Q000378:metabolism*; D004625:Embryo, Nonmammalian / Q000002:abnormalities / Q000473:pathology; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D011485:Protein Binding / Q000235:genetics; D017434:Protein Structure, Tertiary / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity / Q000502:physiology; D014404:Tubulin / Q000378:metabolism; D020798:Two-Hybrid System Techniques; D014981:Xenopus
D005656:Fungal Proteins; D008869:Microtubule-Associated Proteins; D012333:RNA, Messenger; C121041:RO-11 protein, Neurospora crassa; D014404:Tubulin; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; C513190:Pafah1b1 protein, mouse