The Coordination of Local Translation, Membranous Organelle Trafficking, and Synaptic Plasticity in Neurons

Abstract

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.

Statins Use in Alzheimer Disease: Bane or Boon from Frantic Search and Narrative Review

“…Several hundreds of translationally silent mRNAs exist in axons; their activation via stimuli leads to their subsequent protein synthesis specific to that cellular process. miRNAs are located in cell soma, dendrites, and synaptosomes; they control AMPA-type glutamate receptor (AMPAR) along with GABA receptor A (GABA A Rs), crucial for synaptic coordination and long-term potentiation [ 13 ]. Hence, miRNAs are regarded as key regulators of local protein synthesis during synaptic plasticity.…”

“…The role of miRNAs in regulating endoplasmic reticulum (ER) stress is the foundation to unravel, following several studies. Several miRNA families, for instance miR-485, were found to be dysregulated in AD and other neurological diseases [ 11 , 12 , 13 ]. Notably, miRNAs exhibit a crucial role in the pathogenesis of several neurodegenerative diseases, such as AD; they may be either upregulated or downregulated in AD.…”

A critical developmental interval of coupling axon branching to synaptic degradation during neural circuit formation

“…One possibility is that postsynaptic dendrites provide molecular signals to presynaptic axonal branches to limit active zone degradation. Another possibility is that the initiation of spontaneous activity alters local endolysosomal recycling (Tagliatti et al ., 2016) to reduce degradation and favor maintenance, for example through the activity-dependent regulation of local translation of resident mRNAs (Rajgor, Welle and Smith, 2021). A third possibility is the late arrival of presynaptic proteins that protect the active zone, reduce autophagy or alter EGFR function.…”

Mitochondria-Endoplasmic Reticulum Interaction in Central Neurons

“…To meet global and local energy needs, cells regulate mitochondrial movement, fission, fusion, and "parking" mitochondria in every area of the cell. Neuronal mitochondria play a crucial role in maintaining synaptic functions, in particular, by providing local translation both under basic conditions and during plasticity processes [38][39][40]. Rangaraju et.al from Schuman's laboratory used adenosine triphosphate (ATP) inhibitors, local inhibition of mitochondrial compartments, and visualization of newly synthesized proteins, to show that local translation is provided by local mitochondrial clusters.…”