Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
Proc Natl Acad Sci U S A. 2018 Apr 17;115(16):E3827-E3836. doi: 10.1073/pnas.1720956115. Epub 2018 Apr 2.
Memory formation is believed to result from changes in synapse strength and structure. While memories may persist for the lifetime of an organism, the proteins and lipids that make up synapses undergo constant turnover with lifetimes from minutes to days. The molecular basis for memory maintenance may rely on a subset of long-lived proteins (LLPs). While it is known that LLPs exist, whether such proteins are present at synapses is unknown. We performed an unbiased screen using metabolic pulse-chase labeling in vivo in mice and in vitro in cultured neurons combined with quantitative proteomics. We identified synaptic LLPs with half-lives of several months or longer. Proteins in synaptic fractions generally exhibited longer lifetimes than proteins in cytosolic fractions. Protein turnover was sensitive to pharmacological manipulations of activity in neuronal cultures or in mice exposed to an enriched environment. We show that synapses contain LLPs that may underlie stabile long-lasting changes in synaptic structure and function.
记忆的形成被认为是突触强度和结构变化的结果。虽然记忆可能会在生物体内持续一生，但构成突触的蛋白质和脂质会不断更新，其寿命从几分钟到几天不等。记忆维持的分子基础可能依赖于一组长寿命蛋白（LLPs）。虽然已知 LLP 的存在，但突触中是否存在这些蛋白质尚不清楚。我们使用代谢脉冲追踪标记在体内的小鼠和体外培养的神经元进行了无偏筛选，并结合定量蛋白质组学进行了研究。我们鉴定了具有数月或更长半衰期的突触 LLP。突触部分的蛋白质的寿命通常比细胞质部分的蛋白质长。蛋白质周转对神经元培养物或暴露于丰富环境中的小鼠的活性的药理学处理敏感。我们表明，突触含有 LLP，可能是突触结构和功能稳定持久变化的基础。
