Antagonistic contributions of A-type and B-type lamins to LBR localization and dynamics

Lamin B receptor (LBR) is an inner nuclear membrane protein that organizes peripheral heterochromatin and cooperates with lamins to tether chromatin at the nuclear periphery. However, how individual lamin isoforms regulate LBR localization and anchorage remains unclear. Using mouse embryonic fibroblasts lacking all endogenous lamins, we examined how individual lamin isoforms regulate LBR behavior. Expression of lamin B1 or B2 was sufficient to anchor LBR at the nuclear envelope, whereas lamin A expression increased LBR mobility and led to its displacement from the nuclear envelope. This effect was mediated by phosphorylation of LBR and was recapitulated by lamin A overexpression in wild-type cells. Collectively, these findings define isoform-specific and antagonistic roles for A-type and B-type lamins in regulating LBR anchorage at the nuclear envelope. In addition, they indicate a lamin A-dependent mechanism that may reflect a broader developmental process, since LBR and lamin A sequentially tether peripheral heterochromatin during development.