Nuclear lamins and neurobiology.
Much of the work on nuclear lamins during the past 15 years has focused on mutations in LMNA (the gene for prelamin A and lamin C) that cause particular muscular dystrophy, cardiomyopathy, partial lipodystrophy, and progeroid syndromes. These disorders, often called "laminopathies," mainly affect mesenchymal tissues (e.g., striated muscle, bone, and fibrous tissue). Recently, however, a series of papers have identified important roles for nuclear lamins in the central nervous system. Studies of knockout mice uncovered a key role for B-type lamins (lamins B1 and B2) in neuronal migration in the developing brain. Also, duplications of LMNB1 (the gene for lamin B1) have been shown to cause autosome-dominant leukodystrophy. Finally, recent studies have uncovered a peculiar pattern of nuclear lamin expression in the brain. Lamin C transcripts are present at high levels in the brain, but prelamin A expression levels are very low-due to regulation of prelamin A transcripts by microRNA 9. This form of prelamin A regulation likely explains why "prelamin A diseases" such as Hutchinson-Gilford progeria syndrome spare the central nervous system. In this review, we summarize recent progress in elucidating links between nuclear lamins and neurobiology.
Department of Medicine, University of California, Los Angeles, California, USA Department of Human Genetics, University of California, Los Angeles, California, USA Molecular Biology Institute, University of California, Los Angeles, California, USA sgyoung@mednet.ucla.edu lfong@mednet.ucla.edu.
Stephen G
SG
Young
Molecular Biology Institute, University of California, Los Angeles, California, USA.
Hea-Jin
HJ
Jung
Department of Medicine, University of California, Los Angeles, California, USA.
John M
JM
Lee
Department of Medicine, University of California, Los Angeles, California, USA sgyoung@mednet.ucla.edu lfong@mednet.ucla.edu.
Loren G
LG
Fong
D000818:Animals; D006801:Humans; D034882:Lamins / Q000235:genetics* / Q000378:metabolism*; D009446:Neurobiology / Q000379:methods; D034881:Nuclear Lamina / Q000235:genetics* / Q000378:metabolism*
D034882:Lamins