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

How does the amino-terminal domain of LBR reach the nucleus after synthesis in the cytoplasm? Many nuclear proteins contain short stretches of basic amino acids called nuclear localization signals (NLS's) that are responsible for nuclear transport (Garcia-Bustos et al., 1991) . NLS's can direct transport to the nucleus when fused to normally cytoplasmic proteins (Goldfarb et al., 1986) . Most NLS's are similar to the sequence P-K-K-K-R-K-V found in SV-40 large T antigen (Kalderon et al., 1984) . Cytosolic and pore complex proteins that bind to these NLS's target proteins to the nuclear pores and facilitate transport into the nucleus (Silver, 1991; Adam and Gerace, 1991; Moore and Blobel, 1992) . Proteins that contain SV40-type NLS's transported to the nucleus by this mechanism may first be concentrated in the nucleolus after passing through the pores (Breeuwer and Goldfarb, 1990; Meier and Blobel, 1990; Moore and Blobel, 1992 ) and recent evidence has shown that an NLS binding protein may shuttle between the nucleolus and the cytoplasm (Meier and Blobel, 1992) . The LBR amino-terminal domain does not contain a stretch of amino acids similar to the "classical" NLS of SV-40 large T antigen, and the finding that the polypeptide is excluded from the nucleolus also suggests that its nuclear transport does not involve proteins that shuttle between the cytoplasm and nucleolus. It would also be unlikely that translocation to the nucleolus could be achieved for intact LBR where most of the protein would be embedded in the nuclear envelope membranes.