The first membrane spanning region of the lamin B receptor is sufficient for sorting to the inner nuclear membrane

Our finding here that the nucleoplasmic domain of LBR does not contain determinants for sorting to the inner nuclear membrane was unexpected. As mentioned in the introduction, the nucleoplasmic domain, by virtue of its topology, is an attractive candidate for containing LBR's lamin B binding site. However, the finding that the nncleoplasmic domain, although able to localize to the nucleoplasm, is not able to localize to the nuclear rim suggests that, per se, it is unable to compete with LBR for lamin B binding and thereby to attain the status of a "peripheral" membrane protein of the inner nuclear membrane. The ability of the nucleoplasmic domain to localize to the nucleoplasm remains to be investigated. Although this domain does not contain a minimal consensus nuclear localization signal (Chelsky et al., 1989) , the protein is small enough so that it might diffuse into the nucleus (Paine et al., 1975) and localize there by retention. The distribution of the protein throughout the nucleoplasm suggests an affinity for a ubiquitous nuclear component, such as chromatin rather than a peripheral one like the lamina. Affinity for chromatin is consistent with the SPXX motifs that are present in the nucleoplasmic domain and that are common to many DNA binding proteins.