Nuclear lamins: building blocks of nuclear architecture

• Published in: Genes & development 2002-03, Vol.16 (5), p.533-547
• Main Authors: Goldman, Robert D, Gruenbaum, Yosef, Moir, Robert D, Shumaker, Dale K, Spann, Timothy P
• Format: Article
• Language: English
• Subjects: Cardiomyopathy, Dilated - etiology; Cell Cycle; Cell Nucleus - physiology; Cell Nucleus - ultrastructure; DNA Replication; Humans; Lamins; Lipodystrophy - etiology; Muscular Dystrophies - etiology; Nuclear Envelope - metabolism; Nuclear Proteins
• ISSN: 0890-9369; 1549-5477
• DOI: 10.1101/gad.960502

Nuclear lamins were initially identified as the major components of the nuclear lamina, a proteinaceous layer found at the interface between chromatin and the inner nuclear membrane. Due to their position at the periphery of the nucleus, lamins were originally proposed to support the nuclear envelope and provide anchorage sites for chromatin. Recently, the nuclear lamins have also been found in the nucleoplasm. In addition, experimental and genetic evidence suggest that nuclear lamins are involved in a number of other functions including nuclear envelope assembly, DNA synthesis, transcription, and apoptosis. Interestingly, mutations in nuclear lamins have been linked to human diseases. In this review, we describe what is known of the structure and function of lamins and their associated proteins. Further, we speculate about possible mechanisms through which mutations in nuclear lamins give rise to disease. Immunological and structural data originally suggested that the lamins were related to cytoplasmic intermediate filaments (IF). The cloning and sequencing of lamin cDNAs confirmed that lamins have the typical domain structure of IF including an alpha -helical coiled-coil domain flanked by nonhelical domains. Interestingly, analyses of lamin and cytoplasmic IF genomic sequences indicate that nuclear lamins are the progenitors of all IF, with cytoplasmic IF arising through gene duplication.