Rajgor Dipen, Welle Theresa M, Smith Katharine R
Department of Pharmacology, University of Colorado School of Medicine, Aurora, CO, United States.
Front Cell Dev Biol. 2021 Jul 14;9:711446. doi: 10.3389/fcell.2021.711446. eCollection 2021.
Neurons are highly complex polarized cells, displaying an extraordinary degree of spatial compartmentalization. At presynaptic and postsynaptic sites, far from the cell body, local protein synthesis is utilized to continually modify the synaptic proteome, enabling rapid changes in protein production to support synaptic function. Synapses undergo diverse forms of plasticity, resulting in long-term, persistent changes in synapse strength, which are paramount for learning, memory, and cognition. It is now well-established that local translation of numerous synaptic proteins is essential for many forms of synaptic plasticity, and much work has gone into deciphering the strategies that neurons use to regulate activity-dependent protein synthesis. Recent studies have pointed to a coordination of the local mRNA translation required for synaptic plasticity and the trafficking of membranous organelles in neurons. This includes the co-trafficking of RNAs to their site of action using endosome/lysosome "transports," the regulation of activity-dependent translation at synapses, and the role of mitochondria in fueling synaptic translation. Here, we review our current understanding of these mechanisms that impact local translation during synaptic plasticity, providing an overview of these novel and nuanced regulatory processes involving membranous organelles in neurons.
神经元是高度复杂的极化细胞，呈现出非凡程度的空间分隔。在远离细胞体的突触前和突触后位点，局部蛋白质合成被用于持续修饰突触蛋白质组，使蛋白质产生能够快速变化以支持突触功能。突触经历多种形式的可塑性，导致突触强度发生长期、持久的变化，这对于学习、记忆和认知至关重要。现在已经明确，许多突触蛋白的局部翻译对于多种形式的突触可塑性至关重要，并且已经开展了大量工作来破译神经元用于调节活动依赖性蛋白质合成的策略。最近的研究指出了突触可塑性所需的局部mRNA翻译与神经元中膜性细胞器运输之间的协调。这包括利用内体/溶酶体“运输”将RNA共同运输到其作用位点、突触处活动依赖性翻译的调节以及线粒体在为突触翻译提供能量方面的作用。在这里，我们回顾了我们目前对这些在突触可塑性过程中影响局部翻译的机制的理解，概述了这些涉及神经元中膜性细胞器的新颖且细微的调节过程。
