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

The mechanism by which LBR's first transmembrane region would specify sorting from its site of cotranslational insertion, namely the RER and the outer nuclear membrane, to the inner nuclear membrane remains to be investigated. It has been known for some time now (Furthmayr and Marchesi, 1976; Deisenhofer et al., 1985; Bormann et al., 1989; Lemmon et al., 1992 ) that a transmembrane o~-helix is capable of specific interaction with another transmembrane or-helix. One possibility is that the transmembrane u-helix of a specific "sorting receptor" recognizes the transmembrane u-helix of LBR. Lateral movement of the complex along the outer nuclear membrane and the pore membrane domain of the nuclear envelope would carry LBR to the inner nuclear membrane where it might be dissociated from the "sorting receptor" and be retained through its interaction with lamin B and/or other intranuclear components. Another possibility is that the first transmembrane segment of one LBR molecule would specifically interact with the first transmembrane segment of another LBR molecule to form a homodimer and a binding site for lamin B and/or other intranuclear components. Homodimerization could occur immediately following integration into the RER/outer nuclear membrane followed by a random lateral diffusion of the homodimer along the outer nuclear membrane and the pore membrane domain of the nuclear envelope and ligand induced retention at the inner nuclear membrane. Alternatively, LBR monomers may reach the inner nuclear membrane, again via random lateral diffusion along the pore membrane domain of the nuclear envelope followed by a ligand (lamin B and/or intranuclear components) stabilized homodimerization and retention in the inner nuclear mem-brane. Similar scenarios can be considered if the first transmembrane segment of LBR would specifically recognize the transmembrane segment of another integral membrane protein to form a heterodimer.