title: Concentration-dependent lamin assembly and its roles in the localization of other nuclear proteins.
abstract: The nuclear lamina (NL) consists of lamin polymers and proteins that bind to the polymers. Disruption of NL proteins such as lamin and emerin leads to developmental defects and human diseases. However, 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 the NL. Consequently, it has been unclear whether different lamins depend on one another for proper NL assembly and which NL functions are shared by all lamins or are specific to one lamin. Using mouse cells deleted of all or different combinations of lamins, we demonstrate that the assembly of each lamin into the NL depends primarily on the lamin concentration present in the nucleus. When expressed at sufficiently high levels, each lamin alone can assemble into an evenly organized NL, which is in turn sufficient to ensure the even distribution of the nuclear pore complexes. By contrast, only lamin-A can ensure the localization of emerin within the NL. Thus, when investigating the role of the NL in development and disease, it is critical to determine the protein levels of relevant lamins and the intricate shared or specific lamin functions in the tissue of interest.
authors: Department of Biology, Johns Hopkins University, Baltimore, MD 21218 Department of Embryology, Carnegie Institution for Science, Baltimore, MD 21218 Department of Cell and Molecular Biology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611.
authors: Yuxuan
authors: Y
authors: Guo
authors: Youngjo
authors: Y
authors: Kim
authors: Takeshi
authors: T
authors: Shimi
authors: Robert D
authors: RD
authors: Goldman
authors: Yixian
authors: Y
authors: Zheng
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000166:cytology; D034904:Lamin Type A / Q000235:genetics / Q000378:metabolism*; D034921:Lamin Type B / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D034881:Nuclear Lamina / Q000378:metabolism*; D022022:Nuclear Pore; D028861:Nuclear Pore Complex Proteins; D009687:Nuclear Proteins / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering
chemical_list: D034904:Lamin Type A; D034921:Lamin Type B; D008565:Membrane Proteins; D028861:Nuclear Pore Complex Proteins; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; C092710:emerin