The nuclear pore complex (NPC) is a massive molecular machine embedded in the nuclear envelope and controlling traffic into and out of the cell nucleus. Here, we describe some of the outstanding research questions concerning the NPC, its assembly and functions. We also discuss recent findings that link the NPC and its immediate surroundings to the process of cellular aging. Scaffold and barrier nucleoporins are two major types of protein building blocks that make up the NPC. Surprisingly, these two groups of nucleoporins differ dramatically in their turnover rates. Recent work identifies some of the scaffold nucleoporins as the most extremely long-lived proteins in rat brain. Some of the consequences of these findings and new open questions arising from them are discussed. We also consider the evidence for a perturbed permeability barrier in nuclei from old cells and the alteration of nuclear transport pathways under stress conditions. Finally, we describe the connection between premature aging syndromes and the nuclear lamina, a filamentous protein network which underlies the nuclear envelope.
Bibliographical noteFunding Information:
The authors thank Lihi Shaulov for the electron micrographs in Fig. 1 C and Douglass Forbes for many stimulating discussions of NPC assembly. Work in our laboratory is supported by the Israel Science Foundation (grant no. 1072/10 ).
- Extremely long-lived proteins
- Nuclear envelope
- Nuclear permeability
- Nuclear pore complex