Genes to Cognition Program, Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh EH16 4SB, UK.
Genes to Cognition Program, Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh EH16 4SB, UK; School of Computing, Edinburgh Napier University, Edinburgh EH10 5DT, UK.
Neuron. 2022 Dec 21;110(24):4057-4073.e8. doi: 10.1016/j.neuron.2022.09.009. Epub 2022 Oct 5.
The lifetime of proteins in synapses is important for their signaling, maintenance, and remodeling, and for memory duration. We quantified the lifetime of endogenous PSD95, an abundant postsynaptic protein in excitatory synapses, at single-synapse resolution across the mouse brain and lifespan, generating the Protein Lifetime Synaptome Atlas. Excitatory synapses have a wide range of PSD95 lifetimes extending from hours to several months, with distinct spatial distributions in dendrites, neurons, and brain regions. Synapses with short protein lifetimes are enriched in young animals and in brain regions controlling innate behaviors, whereas synapses with long protein lifetimes accumulate during development, are enriched in the cortex and CA1 where memories are stored, and are preferentially preserved in old age. Synapse protein lifetime increases throughout the brain in a mouse model of autism and schizophrenia. Protein lifetime adds a further layer to synapse diversity and enriches prevailing concepts in brain development, aging, and disease.
蛋白质在突触中的寿命对于其信号传递、维持和重塑以及记忆持续时间非常重要。我们在整个小鼠大脑和寿命范围内以单突触分辨率量化了 PSD95 的寿命，PSD95 是兴奋性突触中丰富的突触后蛋白，生成了蛋白质寿命突触组图谱。兴奋性突触的 PSD95 寿命范围很广，从数小时到数月不等，在树突、神经元和脑区具有不同的空间分布。具有短寿命蛋白质的突触在年幼动物和控制本能行为的脑区中更为丰富，而具有长寿命蛋白质的突触则在发育过程中积累，在负责储存记忆的皮层和 CA1 中更为丰富，并在老年时优先保留。在自闭症和精神分裂症的小鼠模型中，大脑中的突触蛋白寿命会全面增加。蛋白质寿命为突触多样性增添了一个新的层面，并丰富了大脑发育、衰老和疾病的主流概念。
