Nuclear transport and the mitotic apparatus: an evolving relationship

Abstract

The trafficking of macromolecules between the cytoplasm and the nucleus is controlled by the nuclear pore complexes (NPCs) and various transport factors that facilitate the movement of cargos through the NPCs and their accumulation in the target compartment. While their functions in transport are well established, an ever-growing number of observations have also linked components of the nuclear transport machinery to processes that control chromosome segregation during mitosis, including spindle assembly, kinetochore function, and the spindle assembly checkpoint. In this review, we will discuss this evolving area of study and emerging hypotheses that propose key roles for components of the nuclear transport apparatus in mitotic progression.

Fig. 1

Schematic representation of the nuclear pore complex (NPC) and its constituents (the nucleoporins/Nups) in vertebrates and in the yeast Saccharomyces cerevisiae. Simplified model of the organization of nucleoporins within the NPC framework in vertebrates (left) and in budding yeast (right). Nucleoporins that belong to a stable sub-complex are enclosed in boxes. Proteins or complexes that are localized at kinetochores during mitosis are circled in red. Other nucleoporins relevant to this review are written in red. Enzymes of the SUMO pathways are highlighted in orange

Fig. 2

Mlp-like proteins are binding sites for SAC proteins. a In metazoan cells the nuclear envelope (gray) disassembles during mitosis and Tpr (human)/Mtor (Drosophila), with attached Mad1 and Mad2, are released from their interphase localization at NPCs (not shown). Tpr or Mtor, potentially within a spindle matrix (pink), appears to play a role in the binding of Mad1, Mad2, and Msp1 to unattached kinetochores (red). Tpr may also bind to kinetochores. b In Aspergillus nidulans, NPCs partially disassembles during mitosis increasing the permeability of the nuclear envelope. However, during this period, AnMlp, AnMad1, and AnMad2 remain intranuclear and are associated with what is thought to be the spindle matrix (pink), and, potentially, kinetochores (not shown). From this location, AnMlp may facilitate the association of AnMad1 and AnMad2 with unattached kinetochores. c S. cerevisiae undergo a closed mitosis, with the nuclear envelope and NPCs remaining intact. Mlp1 and Mlp2 remain associated with the NPC during mitosis and activation of the SAC. SAC activation leads to the recruitment of Mad1 and Mad2 to kinetochores and the loss of detectable Mad2 at NPCs. During SAC arrest, Mad1 cycles between NPCs and kinetochores. Note, in all panels, spindles are depicted as dashed black lines attached to centrosomes/spindle pole bodies

Fig. 3

Schematic representation of the network of interactions between vertebrate NPC-associated and centromere/kinetochore constituents (see text for details). Proteins or complexes that are localized at NPCs during interphase are circled in red (see also Fig. 1). Black outline arrows indicate direct or indirect interactions between the proteins or complexes contributing to their recruitment at kinetochores or centromeres. Red outline arrows indicate NES-mediated recruitment by CRM1 (note that an interaction with CRM1 appears to be required for the initial targeting, but not the maintenance of the CPC at centromeres). Spindle assembly factors whose activity is regulated by RanGTP and importin a/β or importin β are listed (asterisks indicates proteins interacting with importin β only). SUMOylated proteins are also listed. Substrates of Aurora B phosphorylation are also shown (green P). Note that Mad1, Mad2, and Mps1 have not been included in this scheme (see Fig. 2)