Journal
EMBO JOURNAL
Volume 37, Issue 15, Pages -Publisher
WILEY
DOI: 10.15252/embj.201798044
Keywords
organelle aging; protein aging; synaptic vesicle; turnover; vesicle pools
Categories
Funding
- Gottingen Graduate School for Neurosciences, Biophysics, and Molecular Biosciences (GGNB)
- European Molecular Biology Organization [ALTF_7972012]
- Human Frontier Science Program [HFSP_LT000830/2013]
- European Research Council (ERC-2013-CoG NeuroMolAnatomy)
- Deutsche Forschungsgemeinschaft [SFB1190/P09, SFB889/A05, SFB1286/A03, DFG RI 1967 7/1]
- German Federal Ministry of Education and Research [03F0626A]
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Aged proteins can become hazardous to cellular function, by accumulating molecular damage. This implies that cells should preferentially rely on newly produced ones. We tested this hypothesis in cultured hippocampal neurons, focusing on synaptic transmission. We found that newly synthesized vesicle proteins were incorporated in the actively recycling pool of vesicles responsible for all neurotransmitter release during physiological activity. We observed this for the calcium sensor Synaptotagmin 1, for the neurotransmitter transporter VGAT, and for the fusion protein VAMP2 (Synaptobrevin 2). Metabolic labeling of proteins and visualization by secondary ion mass spectrometry enabled us to query the entire protein makeup of the actively recycling vesicles, which we found to be younger than that of non-recycling vesicles. The young vesicle proteins remained in use for up to similar to 24 h, during which they participated in recycling a few hundred times. They were afterward reluctant to release and were degraded after an additional similar to 24-48 h. We suggest that the recycling pool of synaptic vesicles relies on newly synthesized proteins, while the inactive reserve pool contains older proteins.
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