NudE-L, a novel Lis1-interacting protein, belongs to a family of vertebrate coiled-coil proteins.
The LIS1-encoded protein (Lis1) plays a role in brain development because a hemizygous deletion or mutation of the human gene causes neuronal migration disorders, such as Miller-Dieker syndrome (MDS) or isolated lissencephaly sequence (ILS). Using a yeast two-hybrid screen, we have isolated a novel protein that interacts with mouse Lis1 (mLis1) which is termed mouse NudE-like protein (mNudE-L) because of its 49% amino acid conservation with NudE, a protein involved in nuclear migration in Aspergillus nidulans. GST pull-down assays and co-immunoprecipitation of fusion proteins expressed in mammalian cells confirmed the interaction of mLis1 and mNudE-L. mNudE-L gives rise to a approximately 2.3 kb mRNA and encodes an ORF corresponding to approximately 38 kDa protein. The overall amino acid sequence of mNudE-L is 49-95% identical to proteins found in a variety of organisms, thus establishing mNudE-L as a new member of a protein family. The hallmark of this family is an N-terminal region predicted to form a coiled-coil domain. We show that mNudE-L and mLis1 are coexpressed in the postnatal and adult cerebral cortices and in the Purkinje neurons of the cerebellum. In contrast to mLis1, mNudE-L transcripts are absent in the mitral cell layer of the olfactory bulb and in the inward migrating granular neurons of the developing cerebellum. Mutant mLis1 proteins modelling mutations found in human lissencephaly patients fail to interact with mNudE-L, raising the possibility that phenotypic changes result, in part, from the inability of mutant Lis1 proteins to interact with the human NudE-L polypeptide.
Max Planck Institute for Experimental Endocrinology, Feodor-Lynen Strasse 7, 30625, Hannover, Germany.
K J
KJ
Sweeney
A
A
Prokscha
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G
Eichele
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D000595:Amino Acid Sequence; D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism; D002352:Carrier Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D002531:Cerebellum / Q000196:embryology; D018076:DNA, Complementary / Q000378:metabolism; D015723:Gene Library; D005982:Glutathione Transferase / Q000378:metabolism; D017403:In Situ Hybridization; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008969:Molecular Sequence Data; D009154:Mutation; D009830:Olfactory Bulb / Q000196:embryology / Q000378:metabolism; D016366:Open Reading Frames; D010641:Phenotype; D010802:Phylogeny; D017354:Point Mutation; D011233:Precipitin Tests; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution; D014162:Transfection; D020798:Two-Hybrid System Techniques
D002352:Carrier Proteins; D018076:DNA, Complementary; D008869:Microtubule-Associated Proteins; C421108:NDEL1 protein, human; C486015:Ndel1 protein, mouse; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D012313:RNA; D005982:Glutathione Transferase; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; C513190:Pafah1b1 protein, mouse