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

LBR's binding site for lamin B has not yet been identified. During mitosis lamin B appears to be dissociated from LBR 1. Abbreviations used in this paper: HA, hemagglutinin; LBR, lamin B receptor; P, pellet; PCR, polymerase chain reaction; PL, prolactin; pPL, preprolactin; RuBPCase, ribuiose-l,5-bisphosphate carboxylase; S, supernatant; SSRc~, signal sequence receptor cr (Chaudhary, N., G. Blobel, and J. C. Courvalin, unpublished results) in conjunction with the phosphorylation and dephosphorylation at specific sites of the LBR nucleoplasmic domain (Courvalin et al., 1992) . Because of its topology this domain is a candidate for containing LBR's lamin B binding site, which in turn is a candidate for being a determinant for sorting LBR to the inner nuclear membrane. Like other membrane proteins that are newly integrated into the RER membrane system (Bergmann and Singer, 1983; Torrisi and Bonatti, 1985; Torrisi et al., 1987; Powell and Burke, 1990 ) LBR would have access to the inner nuclear membrane through lateral diffusion via the pore membrane domain of the nuclear envelope. Once there, it could simply be tethered by binding to larnin B. Using in vivo expression of full-length, truncated, and chimeric LBR cDNAs we found, however, that it is not the nucleoplasmic domain but the region of the first transmembrane segment that constitutes the primary determinant for sorting of LBR to the inner nuclear membrane.