Extremely long-lived nuclear pore proteins in the rat brain

Abstract

To combat the functional decline of the proteome, cells use the process of protein turnover to replace potentially impaired polypeptides with new functional copies. We found that extremely long-lived proteins (ELLPs) did not turn over in postmitotic cells of the rat central nervous system. These ELLPs were associated with chromatin and the nuclear pore complex, the central transport channels that mediate all molecular trafficking in and out of the nucleus. The longevity of these proteins would be expected to expose them to potentially harmful metabolites, putting them at risk of accumulating damage over extended periods of time. Thus, it is possible that failure to maintain proper levels and functional integrity of ELLPs in nonproliferative cells might contribute to age-related deterioration in cell and tissue function.

Fig. 1. Identification of NUPs and histones as extremely long-lived proteins in mammalian brain

(A) Raw MS1 scans (indicated M/Z ranges) at 0 and 6 months. Distinct peptides for indicated proteins; red indicates ¹⁵N peptide peaks, black ¹⁴N, grey other peptides, and asterisk peaks were successfully identified by MS/MS. (B) Rank ordered distribution of ¹⁵N MS/MS spectral counts (485) grouped as proteins (25) from 12 month brain nuclei and 6 month liver nuclei (inset); histones (black), NUPs (red/light red), and MBP (green). (C) Schematic of NPC. Relative MS1 peak quantitation for each Nup with heavy peptide hits indicated as ¹⁵N /¹⁴N ratios when possible.