A Ribosomal Perspective on Neuronal Local Protein Synthesis

Abstract

Continued mRNA translation and protein production are critical for various neuronal functions. In addition to the precise sorting of proteins from cell soma to distant locations, protein synthesis allows a dynamic remodeling of the local proteome in a spatially variable manner. This spatial heterogeneity of protein synthesis is shaped by several factors such as injury, guidance cues, developmental cues, neuromodulators, and synaptic activity. In matured neurons, thousands of synapses are non-uniformly distributed throughout the dendritic arbor. At any given moment, the activity of individual synapses varies over a wide range, giving rise to the variability in protein synthesis. While past studies have primarily focused on the translation factors or the identity of translated mRNAs to explain the source of this variation, the role of ribosomes in this regard continues to remain unclear. Here, we discuss how several stochastic mechanisms modulate ribosomal functions, contributing to the variability in neuronal protein expression. Also, we point out several underexplored factors such as local ion concentration, availability of tRNA or ATP during translation, and molecular composition and organization of a compartment that can influence protein synthesis and its variability in neurons.

Sex-specific transcriptional signatures in the medial prefrontal cortex underlying sexually dimorphic behavioural responses to stress in rats

“…The DEGs associated with only stress were primarily enriched in synapse-related pathways. Notably, 1 study reported that ribosomes constitutively supply synapses with proteins 51 in the rodent brain, and continued mRNA translation and protein production of ribosomes are essential for neuronal synaptic activity 52 , 53 and homeostasis, 54 suggesting that ribosomes affect synaptic structure and function in the central nervous system. The positive correlation between the number of ribosomes and the thickness of postsynaptic density has been observed in dendrite terminals of neurons, 55 , 56 providing evidence for the importance of ribosomes in ultrastructural synaptic plasticity.…”

Low-dose exposure to malathion and radiation results in the dysregulation of multiple neuronal processes, inducing neurotoxicity and neurodegeneration in mouse

“…Several ribosomal, protein transcription and translation processes, processes related to DNA damage and repair, cell signal activation and transport, which included genes such as Rpl41, Rpl14, RP19, Rp19-ps6, Rps13, Rps10-ps1, and Rpl17, which encode ribosomal proteins involved in large and small ribosomal subunit biogenesis, translation and RNA binding, were affected. Studies have shown that proper ribosomal synthesis, continued mRNA translation, and protein production are critical for maintaining the dendritic tree, dynamic proteome remodelling, synapse formation, axon growth, and synaptic plasticity, and impairment can cause disconnection of neuronal circuitries (Slomnicki et al 2016 ; Dastidar and Nair 2022 ). Furthermore, ribosomal translational dysregulation is among the important events leading to the pathogenesis of disorders such as AD and PD (Ding et al 2005 ).…”

Innovative Family-Based Genetically Informed Series of Analyses of Whole-Exome Data Supports Likely Inheritance for Grammar in Children with Specific Language Impairment

“…The translational efficiency of ribosomes is determined by several factors, including ribosome assembly and how the mRNAs load to the ribosomes. This translational efficiency is variable in the complex neuronal structures creating variability in the protein expression [63]. Deficits in ribosome biogenesis can result in multiple neurodevelopmental disorders.…”