Nuclear Lamins A/C and B1 Provide a Structural Framework That Organizes and Anchors Nuclear Pore Complexes

Nuclear lamin isoforms assemble into fibrous meshworks within the nuclear lamina (NL) where they are associated with nuclear pore complexes (NPCs). Although the lamins and NPCs are major components of the nuclear envelope (NE), little is known about their structural relationships. We used 3D structured illumination microscopy (3D-SIM) and sub-pixel image analysis to show that NPCs are closely associated with lamin fibers in mouse embryonic fibroblasts (MEFs). When lamin A/C (LA/C) or lamin B1 (LB1) are removed by gene knockout, the NPCs retained their association and redistributed with the resulting enlarged lamin meshworks. Cryo-ET revealed that more LA/C than LB1 fibers contacted the nucleoplasmic ring of NPCs. Knockdown of the outer ring nucleoporin ELYS induced NPC clusters that excluded LA/C fibers. Knockdown of the basket nucleoporin TPR reduced the size of LA/C, LB1, and LB2 meshworks while retaining their close association with NPCs. NUP153 knockdown reduced LA/C and B2 meshwork size in wild type (WT) MEFs and caused NPC clustering in nuclei lacking LB1. Therefore, lamins and nucleoporins act together to maintain the organization and distribution of lamin meshworks and NPCs.