concentration-dependent lamin assembly and its role in mitotic spindle assembly

[摘要] Lamins are type-V intermediate filament proteins that polymerize into the nuclear lamina. Mutations in lamin genes cause severe developmental defects and human genetic diseases. Although lamins are known to perform many biological functions, the underlying molecular mechanisms remain poorly understood. The expression of multiple lamins including lamin-A/C, lamin-B1, and lamin-B2 in mammals has made it difficult to study the assembly and function of lamins. Consequently, whether different lamins depend on one another for proper nuclear lamina assembly and which lamin functions are shared by all lamins or are specific to one lamin are unclear. Here I examined the assembly and function of lamins in mouse cells deleted of all or different combinations of lamins. I found the assembly of lamins into the nuclear lamina depended primarily on the total lamin concentration in the nucleus. Each lamin alone can assemble into a smooth nuclear lamina when expressed at a sufficiently high level, which ensures the even distribution of the nuclear pore complexes (NPCs). However, only lamin-A is required for the nuclear retention of emerin. I also found lamins ensure proper NPC distribution and prophase centrosome separation by resisting dynein forces on NPCs. Thus, when studying the roles of lamins in development and diseases, it is critical to establish the amount of each lamin in cells of interest and distinguish the shared and unique functions of lamins. Lamin-regulated centrosome separation also implies a potential mechanism by which lamins regulate spindle assembly and spindle orientation.

[发布机构] Johns Hopkins University

[效力级别] nuclear pore

[关键词] lamin;nuclear pore;centrosome;Biology