Nup50 plays more than one instrument

Abstract

Nup50 is nuclear pore complex component localized to the nuclear side of the pore and in the nucleoplasm. It has been characterized as an auxiliary factor in nuclear transport reactions. Our recent work indicates that it interacts with and stimulates RCC1, the sole guanine nucleotide exchange factor for the GTPase Ran. Here, we discuss how this interaction might contribute to Nup50 function in nuclear transport but also its other functions like control of gene expression, cell cycle and DNA damage repair.

Keywords: DNA repair; Nup50; RCC1; cell cycle; nuclear pore assembly; nuclear trafficking; p27Kip1.

Figure 1.

Nuclear pore complex scheme. Simplified scheme of the nuclear pore complex with the ring structures indicated: inner ring in light blue, cytoplasmic and nuclear rings in light orange, transmembrane nucleoporins in green. In addition, cytoplasmic filaments are in violet, nuclear basket in orange. FG-nucleoporins forming the central channel are in gray.

Figure 2.

Nuclear import and export cycles. An import complex consisting of an NLS-bearing cargo (violet) and importin (green) is formed in the cytoplasm. After NPC passage, RanGTP (blue), formed in the nucleus though the action of RCC1 (white), binds importin, resulting in nuclear cargo release. The importin-RanGTP complex returns to the cytoplasm through the NPC where the Ran GTPase-activating protein (RanGAP1, gray) stimulates GTP hydrolysis, releasing the importin for another import cycle. An export complex consisting of an NES-bearing cargo (pink), exportin (beige) and RanGTP is formed in the nucleus. After NPC passage RanGAP1 stimulates GTP hydrolysis, dissociating the export complex. The import of RanGDP and re-import of the exportin are, for the sake of simplicity, not shown.

Figure 3.

Domain organization of vertebrate Nup50. Scheme showing importin α and RCC1 binding domain (red) as well as the NPC localization domain (green) of Nup50. Also indicated are the importin β binding domain (light orange) and Ran binding domain (light yellow). Amino acid numbers indicating the domain borders refer to the Xenopus protein.

Figure 4.

RCC1 function in mitosis. The establishment of RanGTP gradient by the chromatin (dark blue) bound RCC1 (white) is critical for NPC assembly (upper panel). RanGTP (blue) binding to importin (green) will induce the release of key nucleoporins, allowing NPC formation. The establishment of RanGTP gradient by the chromosome (dark blue) bound RCC1 is also critical for spindle assembly (lower panel). RanGTP (blue) binding to importin will release spindle assembly factors (SAF, pink), allowing spindle assembly (brown). Nup50 (orange) might stimulate RCC1 activity in both cases. By forming a complex with Ran and RCC1, RanBP1 (red) inhibits RCC1 activity in early mitosis.

Figure 5.

Possible implication of Nup50 in nuclear trafficking. By acting as a scaffold at the nuclear basket, Nup50 (orange) could help the dissociation of the import cargo (violet) on the nuclear side. Additionally, by enhancing the RCC1 GEF activity, Nup50 could help to sustain the RanGTP nuclear gradient. This could boost both import cargo dissociation and export cargo formation (pink). The possible interaction between Nup50 and the exportin CRM1 might also enhance nuclear export.