The Nuclear Pore Complex as a Transport Machine

Abstract

nuclear envelope nuclear pore complex nucleoporin ribonucleoprotein nuclear localization signal Nucleocytoplasmic Transport and the Nuclear Pore ComplexUnlike their prokaryotic counterparts, eukaryotic cells separate the nuclear synthesis of DNA and RNA from cytoplasmic protein synthesis with a barrier termed the nuclear envelope (NE).1 The NE is perforated by large proteinaceous assemblies, called nuclear pore complexes (NPCs), which act as the sole gatekeepers controlling the exchange of material between the two locales (reviewed in Ref. 1Wente S.R. Science. 2000; 288: 1374-1377Crossref PubMed Scopus (215) Google Scholar). NPCs are freely permeable to small molecules (such as water and ions), but they restrict the movement of larger molecules (such as proteins and RNAs) across the NE. To overcome this barrier, macromolecules carry specific signals that allow them to access the nucleocytoplasmic transport machinery of the cell. In this way the cell ensures that only selected macromolecules can travel between the nucleus and cytoplasm (reviewed in Ref. 2Mattaj I.W. Englmeier L. Annu. Rev. Biochem. 1998; 67: 265-306Crossref PubMed Scopus (1002) Google Scholar).Operationally, NPCs are composed of proteins called nucleoporins (or Nups) forming the stationary phase for nucleocytoplasmic exchange, whereas the mobile phase consists of soluble transport factors and their cargoes. As nucleocytoplasmic transport is driven by a series of specific interactions between components of both phases, it is frequently difficult to determine which proteins are permanent constituents of the NPC. Nevertheless, to understand how transport occurs, we must characterize the players in both phases and understand how their interplay leads to the coordinated vectorial exchange of macromolecules across the NE. In this review we focus on recent results that shed light on how some of these proteins interact to contribute to the elaborate NPC architecture and its function as a transport machine.Architecture of the NPCNPCs from different organisms share a common fundamental architecture (3Yang Q. Rout M.P. Akey C.W. Mol. Cell. 1998; 1: 223-234Abstract Full Text Full Text PDF PubMed Scopus (281) Google Scholar). These similarities likely provide clues as to the key features common to a functioning transport machine. The NPC is a large octagonally symmetric cylindrical structure. In yeast it estimated to be ∼50 MDa, whereas in metazoans it is over twice this mass (3Yang Q. Rout M.P. Akey C.W. Mol. Cell. 1998; 1: 223-234Abstract Full Text Full Text PDF PubMed Scopus (281) Google Scholar, 4Reichelt R. Holzenburg A. Buhle Jr., E.L. Jarnik M. Engel A. Aebi U. J. PubMed Scopus Google Scholar). that a it be that the NPC of different it that the yeast NPC only different proteins and the NPC a M.P. A. J. 2000; PubMed Scopus Google Scholar). the of how a large complex can be from The to in the of the The NPC is of a cylindrical from which the nucleus and cytoplasm (reviewed in Ref. J. 2000; PubMed Google The of the NPC is in the only is it composed of but is both in a to the NE and in a the cylindrical As from this nucleoporins are in and and are to both the nuclear and cytoplasmic of the NE M.P. A. J. 2000; PubMed Scopus Google Scholar, J. 2000; PubMed Google Scholar, Aebi U. PubMed Scopus Google this with the large of nucleoporins between and it how the NPC can be from a small of the large of nucleoporins them to between of the NPC. for we by NPC in and how they to the of NPC of a NPC from the cytoplasm the cytoplasmic NPC from the the nuclear The of the are by protein by and of both and yeast The of the and are on both the and of the NPC. The of the cytoplasmic nuclear and are on a the of the the of the NPC. by and and Akey of the NPC to the of the nucleoporins the whereas mass is of the to the interactions between nucleoporins M.P. A. J. 2000; PubMed Scopus Google Scholar, J. M. 2000; PubMed Scopus Google Pore and of the Nuclear nuclear envelope is composed of The NE is with the and the the Nuclear are by a of these two the the pore The the with the and proteins to this are termed is the function of they likely a in NPC by the of the pore and as a for the NPC. between from different but as the of pore is it likely that and to be J. PubMed Scopus Google Scholar, M. Jr., Mol. Cell. PubMed Scopus Google the of the pore must be and with the of the that the the this a pore but and are by pore proteins as which is in the 1998; PubMed Scopus Google Scholar, R. M. J. PubMed Google Scholar). a pore protein to be a of the is in NPC R. M. J. PubMed Google Scholar). is the of and this be to the of the NPC and nuclear envelope PubMed Scopus Google Scholar). is a protein in the of in yeast a for in NPC as is NE yeast The and of the NPC is to be the that and the of the NPC. As be the yeast nucleoporins that to this are to both of the NPC M.P. A. J. 2000; PubMed Scopus Google Scholar, Aebi U. PubMed Scopus Google Scholar). only of the nucleoporins is in is likel