The nuclear envelope comprises a distinct compartment at the nuclear periphery that provides a platform for communication between the nucleus and cytoplasm. Signal transfer can proceed by multiple means. Primarily, this is by nucleocytoplasmic trafficking facilitated by NPCs (nuclear pore complexes). Recently, it has been indicated that signals can be transmitted from the cytoskeleton to the intranuclear structures via interlinking transmembrane proteins. In animal cells, the nuclear lamina tightly underlies the inner nuclear membrane and thus represents the protein structure located at the furthest boundary of the nucleus. It enables communication between the nucleus and the cytoplasm via its interactions with chromatin-binding proteins, transmembrane and membrane-associated proteins. Of particular interest is the interaction of the nuclear lamina with NPCs. As both structures fulfil essential roles in close proximity at the nuclear periphery, their interactions have a large impact on cellular processes resulting in affects on tissue differentiation and development. The present review concentrates on the structural and functional lamina–NPC relationship in animal cells and its potential implications to plants.
- nuclear envelope
- nuclear pore complex (NPC)
Nuclear envelope: compartment at the boundary
The NE (nuclear envelope) represents a multifunctional boundary between the nucleus and cytoplasm. It is composed of outer and inner membranes, and a number of integral and associated membrane proteins. In animals, the nuclear lamina tightly associates with the inner nuclear membrane and is linked to the NPCs (nuclear pore complexes), the sole gates for regulated exchange of macromolecules between the nucleus and cytoplasm. Complex interactions between components of this boundary region allow for regulated and synchronized responses to the needs of the cell.
The metazoan lamina is composed of Type V intermediate filament proteins, the lamins, that form a structured meshwork of interconnected ~10 nm filaments linked to the inner membrane . The lamina is thought to contribute to the mechanical stability and elasticity of the NE. Recently, however, it has been shown to be also involved in many fundamental processes, including chromatin organization at the nuclear periphery, transcriptional regulation, DNA replication and NE assembly (reviewed in [2–5]). Last, but not least, the lamina is linked to the NPCs  and thus participates in NPC positioning and trafficking.
Complex relationship between lamins and NPCs
In metazoans, the distribution of NPCs over the NE is controlled and thus non-random. Studies in mammalian cells show that NPCs are stably anchored within the NE, forming immobile arrays with little independent movement . Therefore the actual position of the individual NPC is closely linked to its position within the NPC array. Moreover, the distribution of the NPCs over the NE was shown to be cell-cycle-dependent . Direct involvement of the nuclear lamina in NPC anchoring and positioning was suggested by studies in mammalian cells , Caenorhabditis  and Drosophila . The distribution of the NPCs over the NE correlated with the distribution of A- and B-type lamins in mammalian cells. Whereas lamin B was preferably associated with the areas enriched in NPCs, lamin A/C co-localized with NPC-free islands . The control of the nuclear lamina over the spatial distribution of the NPCs was demonstrated by abnormal clustering of the NPCs in knockdown Caenorhabditis  and Drosophila  mutants. Interestingly, clustered and highly mobile NPCs were detected in yeast cells that lack any apparent lamina structure [11,12].
The following question emerges: what is the nature of the lamina–NPC interaction and the mechanism of lamina-controlled NPC distribution over the NE? Evidence for the direct interaction between the lamina and NPCs were provided by high-resolution scanning electron microscopy of NEs of Xenopus , where lamina filaments were shown to attach directly to the central structures of NPCs. Interestingly, similar connections were observed in tobacco BY-2 cells . The nature of this interaction suggests a possibility that the lamina can directly influence not only NPC position within the NE, but also NPC conformation, and thus directly affect nucleocytoplasmic trafficking. Investigation of the effects of the lamin A mutations causing restrictive dermopathy and Hutchinson–Gilford progeria syndrome indeed showed that disruption of the lamina affects nuclear protein import . The biochemical nature of the lamina–NPC interaction is currently unknown. So far, the only NPC protein (nucleoporin or Nup) shown to date to mediate the lamina–NPC interaction is, surprisingly, Nup153 (homologue of Nup1 in yeast) [15,16]. The N-terminal part of Nup153 locates to the nucleoplasmic ring of the NPC [16,17], where it serves a structural role in nuclear basket formation . The C-terminal part of Nup153 contains the FG-domain region, which suggests an active role of this protein in translocation through the NPC. The FG-domain region of Nup153 was shown to be very dynamic and located to both the nucleoplasmic and cytoplasmic face of the NPC . Therefore it is a little surprising that this FG-domain part of Nup153, rather than the anchored N-terminal part of the protein, was shown to provide the explicit binding site for the lamin interaction . The functional nature of the lamin–Nup153 interaction was provided by testing the mobility of the NPCs within the NE of nuclei assembled in Nup153-depleted nuclear assembly extracts made from Xenopus eggs. In contrast with stably anchored NPCs within normally assembled NEs of Xenopus egg extracts, NPCs lacking Nup153 were mobile . Given the highly dynamic character of Nup153, which was shown to constantly bind and dissociate from the NPC , it is likely that other proteins might be involved in mediating interactions between the lamina and NPCs. Sun1 protein was recognized as an important determinant of NPC distribution across the NE in mammalian cells . Sun proteins function as links between the actin cytoskeleton, the lamins and other nuclear components . Mammalian homologues of Sun1 associate with NPCs but do not contribute to NPC structure. Consequently, clustering of NPCs was detected in response to Sun1 depletion or overexpression. Thus the complex nature of lamina–NPC interactions might involve less obvious candidates that do not play any direct role in NPC structure or transport. So far, the answer to the nature of lamina–NPC interactions and the mechanism of NPC organization remains incomplete.
Seeking the plant lamina
The existence of a nuclear lamina in plant cells has been a long-discussed biological question. No lamin homologues have been identified in the plant genome databases. Biochemical and electron microscopy results were suggestive, but on their own were not sufficient to prove the existence of the lamina in plants [20,21]. Lamina function was originally viewed as purely mechanical and assumed to be substituted by the cell wall in plant cells and yeast. However, the animal lamina has since been demonstrated to play essential roles in many fundamental processes not related to simple structural integrity. These multiple functions of the lamina thus evoke a requirement for a similar compartment at the nuclear periphery in any complex multicellular organism including plants. Intriguingly, nuclei of many plant species frequently contain 10–100 times higher amounts of chromatin than animal nuclei . The position of large chromatin masses is controlled in plant cells and, similarly to animals, heterochromatin is often tethered to the nuclear periphery . The mechanism of this tethering is, however, not known. Recently, we have observed the NE of tobacco BY-2 cells from both the cytoplasmic as well as nucleoplasmic sides by high-resolution scanning electron microscopy . Among other things, we have determined that NPCs are non-randomly distributed over the NE in exponentially growing as well as quiescent tobacco BY-2 cells (Figure 1) . Significantly, we have observed a filamentous lattice closely attached to the inner nuclear membrane of tobacco BY-2 nuclei that was linked to nucleoplasmic rings of the NPCs  and in places had an organization that appeared remarkably similar to the Xenopus oocyte lamina. We decided to call this structure ‘plamina’ (plant lamina) to emphasize both the similarity and difference from the related animal structure. So far, we have no information on the function or the biochemical composition of this lattice which we have observed. However, a few likely candidates with potentially compatible structural features, such as predicted coiled-coil domains, which locate to the nuclear periphery have been identified [24–26] (reviewed in ). As only a small proportion of genes in the Arabidopsis genome were assigned a clear function, it is likely that other proteins having a role in organization of the nuclear periphery will emerge in the future.
The implication of these findings is that there is a need to revise the concept of plant inner nuclear membrane structure and composition. It is now essential to define which proteins constitute the protein lattice attached to the inner nuclear membrane in tobacco BY-2 cells and decipher the entire network of proteins linked to the inner nuclear membrane in plants. Recently, Sun proteins were identified in Arabidopsis as the first exclusive plant inner nuclear membrane proteins . However, much more effort will be needed to elucidate the mechanisms of NPC positioning, chromatin organization and NE assembly to formulate a more complete picture of the complex processes at the nuclear periphery in animal and plant cells.
This work was supported by the Biotechnology and Biological Sciences Research Council (BBSRC) [grant number BBE0157351].
Organelle Biogenesis and Positioning in Plants: Biochemical Society Annual Symposium No. 77 held at University of Chester, U.K., 16–18 December 2009. Organized and Edited by David Evans and Chris Hawes (Oxford Brookes University, U.K.).
Abbreviations: NE, nuclear envelope; NPC, nuclear pore complex
- © The Authors Journal compilation © 2010 Biochemical Society