The role of human and Drosophila NXF proteins in nuclear mRNA ...

1.1.3 The nuclear pore complex
Introduction 8
NPCs are large proteinaceous structures perforating the nuclear envelope (see:
Fahrenkrog and Aebi, 2002; Gorlich and Kutay, 1999; Ohno et al., 1998; Rout and
Aitchison, 2001; Vasu and Forbes, 2001; for reviews about NPC architecture, structure and
function, and references therein). They form aqueous channels through which all
nucleocytoplasmic transport processes occur. NPCs are freely permeable to small
molecules (such as water and ions) but act as highly selective permeability barriers for
larger molecules (> 40 kDa). To overcome this permeability barrier, macromolecules must
carry specific signals which enable them to access the active transport machinery of the
cell. During active transport (also called facilitated translocation), the aqueous channel of
the NPC, which is ~ 9 nm in diameter when at rest, can expand to about 25 nm. There are
about 3000-5000 NPCs in a growing mammalian cell, each allowing the translocation of
more than 10-20 MDa of material per second (Ribbeck and Gorlich, 2001).
NPCs are eight-fold symmetric assemblies composed of a central core structure
with extensions that form the cytoplasmic filaments and the nuclear basket (Figure 1).
Vertebrate NPCs have a mass of approximately 125 MDa and are composed of 30-50
different proteins which are often collectively called nucleoporins. Nucleoporins are
usually present in 8, 16 or 32 copies per NPC. Many nucleoporins contain characteristic
domains featuring multiple repeats of short sequences ending in the amino acids
phenylalanine and glycine (FG-repeats). These FG-repeats are thought to mediate
interactions with soluble transport receptors. Some specific nucleoporins have been shown
to be essential for only specific import or export pathways, suggesting that not all FGrepeats
are functionally equivalent.
A B
Figure 1: Schematic representation of the NPC
(A) 3D model of the NPC. The central transmembrane core as well as nuclear and cytoplasmic
extensions are shown. From Ohno et al. (1998). (B) Localization of some vertebrate nucleoporins on the
different NPC domains. The nucleoporins tested for NXF binding in paper 1 (CAN, Nup98, p62 and
Nup153)(Herold et al., 2000) are also represented (courtesy of Gwenael Rabut, modified from
Fahrenkrog and Aebi, 2002).