14-3-3 epsilon is important for neuronal migration by binding to NUDEL: a molecular explanation for Miller–Dieker syndrome

Speaker :林純羽

Time :12/10/03

Place :602 Room

ABSTRACT:

Deletions of 17p13.3, including the Lis1 gene, results in a human neuronal migration disorders isolated lissencephaly sequence (ILS) and its more severe form Miller–Dieker syndrome (MDS). Children with MDS have larger genetic deletion than ILS, but the specific genetic basis for MDS remains unknown. The gene encoding for 14-3-3e (YWHAE) is usually deleted in patients with MDS¹. Mice deficient in Ywhae are found to have defects in brain development and neuronal migration in a dose-dependent fashion, and those mice with deletions of both genes have even more migration defects .14-3-3e binds to CDK5/p35-phosphorylated NUDEL and thus protect the complex from dephosphorylation by phosphotases. Deficiency of 14-3-3e influences distribution of NUDEL and LIS1, consistent with reduction of cytoplasmic dynein function. These results suggests that 14-3-3emay have functional importance in neuronal development by maintaining phosphorylation of NUDEL, and provide a molecular explanation for the differences in severity of human neuronal migration defects with 17p13.3 deletions.

*Reference:

1.     Cardoso, C. et al. Refinement of a 400 kb critical region allows genotypic differentiation between isolated lissencephaly, Miller-Dieker syndrome and other phenotypes secondary to deletions of 17p13.3. Am. J. Hum. Genet. 72, 918-930 (2003).

2.      Toyo-oka K et al. 14-3-3epsilon is important for neuronal migration by binding to NUDEL: a molecular explanation for Miller-Dieker syndrome. Nat Genet. 34(3), 274-85(2003).