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

Jung HJ,Nobumori C,Goulbourne CN,Tu Y,Lee JM,Tatar A,Wu D,Yoshinaga Y,de Jong PJ,Coffinier C,Fong LG,Young SG

doi

10.1073/pnas.1303916110

subject

Has Abstract

pub_date

2013-05-21 00:00:00

pages

E1923-32

issue

21

eissn

0027-8424

issn

1091-6490

pii

1303916110

journal_volume

110

pub_type

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