title: Identification of long-lived proteins reveals exceptional stability of essential cellular structures.
abstract: Intracellular proteins with long lifespans have recently been linked to age-dependent defects, ranging from decreased fertility to the functional decline of neurons. Why long-lived proteins exist in metabolically active cellular environments and how they are maintained over time remains poorly understood. Here, we provide a system-wide identification of proteins with exceptional lifespans in the rat brain. These proteins are inefficiently replenished despite being translated robustly throughout adulthood. Using nucleoporins as a paradigm for long-term protein persistence, we found that nuclear pore complexes (NPCs) are maintained over a cell's life through slow but finite exchange of even its most stable subcomplexes. This maintenance is limited, however, as some nucleoporin levels decrease during aging, providing a rationale for the previously observed age-dependent deterioration of NPC function. Our identification of a long-lived proteome reveals cellular components that are at increased risk for damage accumulation, linking long-term protein persistence to the cellular aging process. PAPERCLIP:
authors.affiliation: Molecular and Cell Biology Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
authors.forename: Brandon H
authors.initials: BH
authors.lastname: Toyama
authors.affiliation: Department of Chemical Physiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Jeffrey N
authors.initials: JN
authors.lastname: Savas
authors.affiliation: Department of Chemical Physiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Sung Kyu
authors.initials: SK
authors.lastname: Park
authors.affiliation: Department of Embryology, Carnegie Institution for Science, Baltimore, MD 21218, USA; Department of Biology, The Johns Hopkins University, Baltimore, MD 21218, USA.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Harris
authors.affiliation: Department of Embryology, Carnegie Institution for Science, Baltimore, MD 21218, USA.
authors.forename: Nicholas T
authors.initials: NT
authors.lastname: Ingolia
authors.affiliation: Department of Chemical Physiology, The Scripps Research Institute, La Jolla, CA 92037, USA. Electronic address: jyates@scripps.edu.
authors.forename: John R
authors.initials: JR
authors.lastname: Yates
authors.affiliation: Molecular and Cell Biology Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA. Electronic address: hetzer@salk.edu.
authors.forename: Martin W
authors.initials: MW
authors.lastname: Hetzer
mesh_terms: D000818:Animals; D001921:Brain / Q000166:cytology* / Q000378:metabolism; D016922:Cellular Senescence; D009457:Neuroglia / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D022022:Nuclear Pore / Q000378:metabolism; D028861:Nuclear Pore Complex Proteins / Q000378:metabolism*; D014176:Protein Biosynthesis; D020543:Proteome / Q000378:metabolism*; D051381:Rats
chemical_list: D028861:Nuclear Pore Complex Proteins; D020543:Proteome