The nuclear periphery

In recent years, definitions of the nuclear periphery have become increasingly blurred with the realization that nuclear envelope (NE) and nuclear pore complex (NPC) components interact with and influence the behavior of both nuclear and cytoplasmic structures. The Minisymposium on the Nuclear Periphery reflected this evolving outlook by bringing together an eclectic group of researchers working on a variety of problems related to the biology of the NE/NPC. A. Szymborska (Ellenberg laboratory, European Molecular Biology Laboratory, Heidelberg) described how emerging techniques in superresolution light microscopy can be used to define the disposition of NPC components with precision in the range of nanometers. This approach permitted the first visualization of the radial substructure of the NPC by light microscopy and was able to resolve distinct members of an NPC subcomplex (the Nup107-160/Y complex). This has provided new insights into the orientation of this complex within the NPC. L. Lu (Kirchhausen laboratory, Harvard Medical School, Boston) raised the controversial issue of how NPCs become incorporated into the reforming NE at the end of mitosis. Using a combination of three-dimensional live-cell imaging and electron microscope tomography, he showed that newly segregated chromatids become coated by planar membrane sheets derived from the peripheral endoplasmic reticulum prior to NPC assembly. This suggests that mitotic and interphase NPC assembly may follow similar pathways (Lu et al., 2011 ). D. Osorio (Gomes laboratory, Universite Pierre et Marie Curie, Paris) described a small interfering RNA (siRNA)-based screen that revealed a role for Ndc1, an NPC membrane protein, in the positioning of the nucleus relative to the centrosome during fibroblast migration. His data indicate that the interaction of Ndc1 with Sun2, a constituent of LINC (LInker of the Nucleoskeleton and Cytoskeleton) complexes might regulate nuclear positioning and cell migration. D. Hu (Vallee laboratory, Columbia University, New York) focused on the cell cycle–dependent nuclear oscillation in neural progenitor cells. This process, termed interkinetic nuclear migration (INM), involves dynein-driven migration of the nucleus toward the apical surface of the neocortex in G2 (Tsai et al., 2010 ). Interestingly, in vivo siRNA-mediated depletion of factors previously implicated in dynein recruitment to the NE during G2 in nonneuronal cells, namely BicD2 (Splinter et al., 2010 ) and Nup133 (Bolhy et al., 2011 ), successively impaired INM in G2. These findings strongly support a role for dynein recruitment to the NE in apical nuclear migration during INM and provide insight into the mechanism of cell cycle control. H. Horn (Stewart laboratory, Institute of Medical Biology, Singapore) reported on the role of nesprin-4 (Nesp4), an outer nuclear membrane protein and LINC complex component. Nesp4 functions as an adaptor for kinesin-1 and is expressed in certain epithelial cells, including hair cells of the inner ear (Roux et al., 2009 ). Derivation of Nesp4-deficient mice reveals that this protein is required for the basal positioning of nuclei in outer hair cells. In the absence of Nesp4, outer hair cells are lost through apoptosis, resulting in progressive hearing loss. Y. Kim (Zheng laboratory, Carnegie Institute for Science, Baltimore) unexpectedly reported that lamin B1− and B2− double-knockout embryonic stem cells (ESCs), despite expressing no other type of lamin (A/C or B3), are indistinguishable from wild-type cells and are fully capable of differentiating toward the trophectoderm lineage. Furthermore, gene-expression analyses revealed that B-type lamins are not required for the silencing of their bound genes that are required for lineage specification in differentiating ESCs. Remarkably, lamin B double-knockout mice develop to term, albeit with defects in multiple organs (Kim et al., 2011 ). Clearly, this study is going to change our view of nuclear lamina function in both health and disease. Taken together, the studies described in this minisymposium impact a number of areas of cell and developmental biology. There is little doubt that they will provide the foundation for future work in this rapidly evolving field. We look forward to seeing the fruits of this work at future ASCB meetings.