Nucleocytoplasmic trafficking

Abstract

Nucleocytoplasmic trafficking describes the process whereby molecules destined for the nucleoplasm or cytoplasm move across the nuclear envelope. This transport regulates transcription and translation by respective control of transnuclear movements of transcription factors and messenger RNA. Transport across the nuclear envelope occurs through large MDa pores embedded in the inner and outer nuclear membranes, and is a dynamic, adaptable process modulated by biochemical and biophysical cellular milieus. The present review discusses current understanding of the composition and function of the nuclear pore complex through which transport occurs; regulatory elements within molecular cargo that influence its movement into and out of the nucleus; transport associated proteins that guide the cargo across the nuclear envelope; and factors responsible for modulating nucleocytoplasmic transport. Key Words: Nuclear pore complex; Nuclear transport Nucleocytoplasmic traffickingRandolph S Faustino PhD 1 , Grant N Pierce PhD 2 NuCleoCytoPlaSmiC tRaFFiCKiNGNuclear transport is a complex process involving soluble, cytosolic machinery and membrane-bound components. Molecules that localize from cytosolic to nucleoplasmic compartments and vice versa must cross both the outer and inner nuclear membranes of the nuclear envelope (NE) to reach their destination. For this purpose, a large multiproteinaceous structure known as the nuclear pore complex (NPC) spans both membranes of the NE and serves as the gateway through which molecules transit (1-10). the NPC Structure and compositionElectron microscopy of an NE in cross-section demonstrates how the NPC serves as a proteinaceous 'rivet' connecting both outer and inner nuclear membranes of the NE. Immunocytochemistry using mAb414, an antibody that recognizes NPC proteins or nucleoporins (nups), demonstrates intense staining of the nucleus as well as cytoplasmic annulate lamellae (Figure 1). Confocal microscopy of smooth muscle cells illustrates regular distribution of NPCs across the surface of the NE. The NPC is a dynamic and highly regulated structure, which shows a high degree of evolutionary conservation across various species (7). Most of the information on NPC composition and architecture has been garnered from yeast (10) and Xenopus (11,12); however, the primary focus of this section will be on mammalian NPCs.Mammalian NPCs are approximately 125 MDa and composed of 30 to 32 discrete nups that occur in redundant groupings within the pore (7). Overall, the NPC is approximately 120 nm in diameter and possesses an axial depth of approximately 70 nm. It is composed of eight multimeric subunits arranged in an annular configuration that can be visualized as a distinctive barrel-like shape. This structural conformation leaves a functionally dynamic aqueous central channel approximately 9 nm to 11 nm in diameter under normal conditions (13,14). Electron microscopy of prepared NEs illustrates the octagonal symmetry of the pore when viewed en face. The central pore can dilate to accommodate ...