NudE-L, a novel Lis1-interacting protein, belongs to a family of vertebrate coiled-coil proteins.

The LISI-encoded protein (Lis 1) 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 Lis 1 (mLis 1) 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 mLis 1 and mNudE-L. mNudE-L gives rise to a similar to2.3 kb mRNA and encodes an ORF corresponding to similar to 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 mLis 1 are coexpressed in the postnatal and adult cerebral cortices and in the Purkinje neurons of the cerebellum. In contrast to mLis 1, 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 mLis 1 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 Lis 1 proteins to interact with the human NudE-L polypeptide. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved