title: Farnesylation of lamin B1 is important for retention of nuclear chromatin during neuronal migration.
abstract: The role of protein farnesylation in lamin A biogenesis and the pathogenesis of progeria has been studied in considerable detail, but the importance of farnesylation for the B-type lamins, lamin B1 and lamin B2, has received little attention. Lamins B1 and B2 are expressed in nearly every cell type from the earliest stages of development, and they have been implicated in a variety of functions within the cell nucleus. To assess the importance of protein farnesylation for B-type lamins, we created knock-in mice expressing nonfarnesylated versions of lamin B1 and lamin B2. Mice expressing nonfarnesylated lamin B2 developed normally and were free of disease. In contrast, mice expressing nonfarnesylated lamin B1 died soon after birth, with severe neurodevelopmental defects and striking nuclear abnormalities in neurons. The nuclear lamina in migrating neurons was pulled away from the chromatin so that the chromatin was left "naked" (free from the nuclear lamina). Thus, farnesylation of lamin B1--but not lamin B2--is crucial for brain development and for retaining chromatin within the bounds of the nuclear lamina during neuronal migration.
authors: Molecular Biology Institute, Department of Medicine, and Department of Human Genetics, University of California, Los Angeles, CA 90095, USA.
authors: Hea-Jin
authors: HJ
authors: Jung
authors: Chika
authors: C
authors: Nobumori
authors: Chris N
authors: CN
authors: Goulbourne
authors: Yiping
authors: Y
authors: Tu
authors: John M
authors: JM
authors: Lee
authors: Angelica
authors: A
authors: Tatar
authors: Daniel
authors: D
authors: Wu
authors: Yuko
authors: Y
authors: Yoshinaga
authors: Pieter J
authors: PJ
authors: de Jong
authors: Catherine
authors: C
authors: Coffinier
authors: Loren G
authors: LG
authors: Fong
authors: Stephen G
authors: SG
authors: Young
mesh_terms: D000818:Animals; D001921:Brain / Q000196:embryology*; D002465:Cell Movement / Q000502:physiology*; D002843:Chromatin / Q000235:genetics / Q000378:metabolism*; D034921:Lamin Type B / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D034881:Nuclear Lamina / Q000235:genetics / Q000378:metabolism*; D017368:Protein Prenylation / Q000502:physiology*
chemical_list: D002843:Chromatin; D034921:Lamin Type B
keywords: CaaX motif; genetically modified mouse models; nucleokinesis; posttranslational modification
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