title: Age-dependent deterioration of nuclear pore complexes causes a loss of nuclear integrity in postmitotic cells.
abstract: In dividing cells, nuclear pore complexes (NPCs) disassemble during mitosis and reassemble into the newly forming nuclei. However, the fate of nuclear pores in postmitotic cells is unknown. Here, we show that NPCs, unlike other nuclear structures, do not turn over in differentiated cells. While a subset of NPC components, like Nup153 and Nup50, are continuously exchanged, scaffold nucleoporins, like the Nup107/160 complex, are extremely long-lived and remain incorporated in the nuclear membrane during the entire cellular life span. Besides the lack of nucleoporin expression and NPC turnover, we discovered an age-related deterioration of NPCs, leading to an increase in nuclear permeability and the leaking of cytoplasmic proteins into the nucleus. Our finding that nuclear "leakiness" is dramatically accelerated during aging and that a subset of nucleoporins is oxidatively damaged in old cells suggests that the accumulation of damage at the NPC might be a crucial aging event.
authors.affiliation: Salk Institute for Biological Studies, Molecular and Cell Biology Laboratory, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: Maximiliano A
authors.initials: MA
authors.lastname: D'Angelo
authors.forename: Marcela
authors.initials: M
authors.lastname: Raices
authors.forename: Siler H
authors.initials: SH
authors.lastname: Panowski
authors.forename: Martin W
authors.initials: MW
authors.lastname: Hetzer
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans; D002467:Cell Nucleus / Q000502:physiology*; D015536:Down-Regulation; D051379:Mice; D008938:Mitosis; D022022:Nuclear Pore / Q000502:physiology*; D028861:Nuclear Pore Complex Proteins / Q000502:physiology; D051381:Rats
chemical_list: D028861:Nuclear Pore Complex Proteins