Abstract
The lamin B receptor (LBR) is a polytopic integral membrane protein localized exclusively in the inner nuclear membrane domain of the nuclear envelope. Its cDNA deduced primary structure consists of a highly charged amino-terminal domain of 205 residues that faces the nucleoplasm followed by a hydrophobic domain with eight potential transmembrane segments. To identify determinants that sort LBR from its site of integration (RER and outer nuclear membrane) to the inner nuclear membrane, we prepared full-length, truncated, and chimeric cDNA constructs of chick LBR, transfected these into mammalian cells and detected the expressed protein by immunofluorescence microscopy using appropriate antibodies. Surprisingly, we found that the determinants for sorting of LBR to the inner nuclear membrane reside in a region comprising its first transmembrane sequence plus flanking residues on either side. The other transmembrane regions as well as the nucleoplasmic domain are not required for sorting. We propose that the first transmembrane segment of LBR interacts specifically with another transmembrane segment and consider several mechanisms by which such specific interaction could result in sorting to the inner nuclear membrane.
Highlights
U 'SING solution and solid state binding assays, isolated lamin B from turkey nuclei has previously been shown to bind to an integral membrane protein of the nuclear envelope termed the lamin B receptor (LBR)1 or p58 0Vorman et al, 1988)
Our data here indicate that the first transmembrane region containing the first transmembrane segment plus flanking residues on either side contribute the determinants that sort LBR 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
Summary
U 'SING solution and solid state binding assays, isolated lamin B from turkey nuclei has previously been shown to bind to an integral membrane protein of the nuclear envelope termed the lamin B receptor (LBR) or p58 (because of its apparent molecular weight in SDSPAGE) 0Vorman et al, 1988). 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 be tethered by binding to larnin B. Using in vivo expression of full-length, truncated, and chimeric LBR cDNAs we found, 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
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
