The nuclear pore complex: Toward its molecular architecture, structure, and function

Abstract

The nuclear pore complex (NPC) is a ∼120 MDa macromolecular assembly embedded in the double-membraned nuclear envelope (NE) that mediates bidirectional molecular trafficking between the cytoplasm and the nucleus of interphase cells. Electron microscopy (EM) of negatively stained and frozen-hydrated specimens combined with three-dimensional (3-D) reconstruction has yielded the architecture of the basic framework of the NPC, and a number of specimen preparation methods and microscopy techniques have revealed the structure of distinct peripheral NPC components such as the cytoplasmic and nuclear ring, the cytoplasmic filaments, and the nuclear basket. Recently, significant progress has been made toward identifying, characterizing, and cloning and sequencing NPC proteins. However, to date only about two dozen NPC proteins, called nucleoporins, have been identified, a number accounting for less than 15% of the NPC mass. Some of these nucleoporins have been localized within the 3-D structure of the NPC; thus the molecular architecture of the NPC is starting to emerge. Nevertheless, the 3-D structure and functional significance of the different structural components and proteins of the NPC remain to be established. Relatively little is known about the molecular mechanisms underlying nucleocytoplasmic transport through the NPC. However, over the past few years there have been some advances in establishing the signals, receptors, and factors mediating nuclear import of proteins and snRNP particles, and nuclear export of RNAs and RNP particles. These functional studies have indicated that there may exist multiple signaling pathways for these different processes and substrates. Here we review recent advances toward the 3-D structure and molecular architecture of the NPC, and the molecular basis of nucleocytoplasmic transport of proteins, RNAs, and RNP particles through the NPC.