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.
journal_name
Proc Natl Acad Sci U S Aauthors
Jung HJ,Nobumori C,Goulbourne CN,Tu Y,Lee JM,Tatar A,Wu D,Yoshinaga Y,de Jong PJ,Coffinier C,Fong LG,Young SGdoi
10.1073/pnas.1303916110subject
Has Abstractpub_date
2013-05-21 00:00:00pages
E1923-32issue
21eissn
0027-8424issn
1091-6490pii
1303916110journal_volume
110pub_type
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