title: A-type Lamins Form Distinct Filamentous Networks with Differential Nuclear Pore Complex Associations.
abstract: The nuclear lamina is a universal feature of metazoan nuclear envelopes (NEs) [1]. In mammalian cells, it appears as a 10-30 nm filamentous layer at the nuclear face of the inner nuclear membrane (INM) and is composed primarily of A- and B-type lamins, members of the intermediate filament family [2]. While providing structural integrity to the NE, the lamina also represents an important signaling and regulatory platform [3]. Two A-type lamin isoforms, lamins A and C (LaA and LaC), are expressed in most adult human cells. Encoded by a single gene, these proteins are largely identical, diverging only in their C-terminal tail domains. By contrast with that of LaC, the unique LaA tail undergoes extensive processing, including farnesylation and endo-proteolysis [4, 5]. However, functional differences between LaA and LaC are still unclear. Compounding this uncertainty, the structure of the lamina remains ill defined. In this study, we used BioID, an in vivo proximity-labeling method to identify differential interactors of A-type lamins [6]. One of these, Tpr, a nuclear pore complex (NPC) protein, is highlighted by its selective association with LaC. By employing superresolution microscopy, we demonstrate that this Tpr association is mirrored in enhanced interaction of LaC with NPCs. Further superresolution studies visualizing both endogenous A- and B-type lamins have allowed us to construct a nanometer-scale model of the mammalian nuclear lamina. Our data indicate that different A- and B-type lamin species assemble into separate filament networks that together form an extended composite structure at the nuclear periphery providing attachment sites for NPCs, thereby regulating their distribution.
authors.affiliation: Laboratory of Nuclear Dynamics and Architecture, Institute of Medical Biology, 8A Biomedical Grove, Immunos, Singapore 138648, Singapore. Electronic address: wei.xie@imb.a-star.edu.sg.
authors.forename: Wei
authors.initials: W
authors.lastname: Xie
authors.affiliation: Laboratory of Developmental and Regenerative Biology, Institute of Medical Biology, 8A Biomedical Grove, Immunos, Singapore 138648, Singapore.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Chojnowski
authors.affiliation: IPAL UMI 2955 (CNRS, UPMC, UJF, IMT, I2R, NUS), BioInformatics Institute, Agency for Science, Technology and Research (A(∗)STAR), 30 Biopolis Street, 07-01 Matrix, Singapore 138671, Singapore.
authors.forename: Thomas
authors.initials: T
authors.lastname: Boudier
authors.affiliation: Microscopy Unit, Institute of Medical Biology, 8A Biomedical Grove, Immunos, Singapore 138648, Singapore.
authors.forename: John S Y
authors.initials: JS
authors.lastname: Lim
authors.affiliation: Laboratory of Neural Stem Cells, Institute of Medical Biology, 8A Biomedical Grove, Immunos, Singapore 138648, Singapore.
authors.forename: Sohail
authors.initials: S
authors.lastname: Ahmed
authors.affiliation: Laboratory of Developmental and Regenerative Biology, Institute of Medical Biology, 8A Biomedical Grove, Immunos, Singapore 138648, Singapore.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Ser
authors.affiliation: Laboratory of Developmental and Regenerative Biology, Institute of Medical Biology, 8A Biomedical Grove, Immunos, Singapore 138648, Singapore.
authors.forename: Colin
authors.initials: C
authors.lastname: Stewart
authors.affiliation: Laboratory of Nuclear Dynamics and Architecture, Institute of Medical Biology, 8A Biomedical Grove, Immunos, Singapore 138648, Singapore. Electronic address: brian.burke@imb.a-star.edu.sg.
authors.forename: Brian
authors.initials: B
authors.lastname: Burke
mesh_terms: D006801:Humans; D007382:Intermediate Filaments / Q000378:metabolism*; D034904:Lamin Type A / Q000378:metabolism*; D022022:Nuclear Pore / Q000502:physiology*; D028861:Nuclear Pore Complex Proteins / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism
chemical_list: D034904:Lamin Type A; D028861:Nuclear Pore Complex Proteins; D011518:Proto-Oncogene Proteins; C073597:TPR protein, human
keywords: intermediate filaments; nuclear envelope; nuclear lamina; super-resolution microscopy