The amino-terminal domain of the lamin B receptor is a nuclear envelope targeting signal

It is also possible that the LBR amino-terminal domain can accumulate in the nucleus by diffusion and ligand binding. As fluorescent-labeled dextrans with molecular masses <60 kD can passively diffuse through the nuclear pore complexes (Paine et al., 1975) , the LBR amino-terminal domain is small enough (~22.5 kD) to enter the nucleus by diffusion. If LBR amino-terminal polypeptide can diffuse through the nuclear pores, its concentration in the nucleus may result from its ability to bind to nuclear components. In vitro experiments have shown that LBR binds to lamin B (Worman et al., 1988) , and it is possible that the lamin B binding domain of the protein is in the nucleoplasmic amino terminus. If the free amino-terminal domain were binding only to lamin B in vivo, a nuclear rim fluorescence pattern would be expected on immunofluorescence microscopy. The diffuse localization in the nucleus observed when free aminoterminal domain is expressed in transfected cells argues against lamin B binding being solely responsible for nuclear accumulation of this polypeptide. Therefore, in the nucleus in vivo, the LBR amino-terminal polypeptide may bind to other nuclear components in addition to lamin B. The aminoterminal domain of LBR also possesses characteristics of a chromatin binding protein (Worman et al., 1990) including a basic pI and three S/T-P-X-X motifs that have the capacity to bind to DNA (Suzuki et al., 1989) . The diffuse staining of the nucleus in immunofluorescence microscopy suggests that the LBR amino-terminal domain may bind to chromatin and that this binding, in addition to lamin B binding, may be responsible for its concentration in the nucleus. When embedded in the ER membrane via a transmembrane segment after synthesis, the cytoplasmically exposed aminoterminal domain of LBR may cause the protein to diffuse through the interconnected proteolipid bilayers of the ER, outer nuclear and nuclear pore membranes to reach the inner nuclear membrane where the exposed amino terminus can bind to intranuclear components such as chromatin or lamin B.