Nuclear lamins: building blocks of nuclear architecture

  1. Robert D. Goldman1,3,4,
  2. Yosef Gruenbaum2,3,
  3. Robert D. Moir1,
  4. Dale K. Shumaker1, and
  5. Timothy P. Spann1
  1. 1Northwestern University Medical School, Department of Cell and Molecular Biology, Chicago, Illinois 60611, USA; 2The Hebrew University of Jerusalem, Department of Genetics, Institute of Life Sciences, Jerusalem 91904, Israel; 3The Marine Biological Laboratory, Woods Hole, Massachusetts 02543, USA

This extract was created in the absence of an abstract.

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 (Fawcett 1966). 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 (Fig. 1). 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) (Aebi et al. 1986; Goldman et al. 1986). The cloning and sequencing of lamin cDNAs confirmed that lamins have the typical domain structure of IF including an α-helical coiled-coil domain flanked by nonhelical domains (Fisher et al. 1986; McKeon et al. 1986). 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 (Riemer et al. 2000).

Figure 1.

Illustration depicting the various proposed interactions of lamins with inner nuclear membrane proteins, nuclear pores, and various other nucleoplasmic factors. The lamins are depicted as being concentrated in the lamina (thick red lines) and also distributed throughout the nucleoplasm (thinner red lines). The filamentous nature of the lamins, especially in the nucleoplasm, remains hypothetical. Some of the known LEM domain proteins, including LAPs 2α and β, MAN1, otefin, and …

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