Compartmentalized Signaling in Neurons: From Cell Biology to Neuroscience

Abstract

Neurons are the largest known cells, with complex and highly polarized morphologies. As such, neuronal signaling is highly compartmentalized, requiring sophisticated transfer mechanisms to convey and integrate information within and between sub-neuronal compartments. Here, we survey different modes of compartmentalized signaling in neurons, highlighting examples wherein the fundamental cell biological processes of protein synthesis and degradation, membrane trafficking, and organelle transport are employed to enable the encoding and integration of information, locally and globally within a neuron. Comparisons to other cell types indicate that neurons accentuate widely shared mechanisms, providing invaluable models for the compartmentalization and transfer mechanisms required and used by most eukaryotic cells.

Topoisomerase 2β-dependent nuclear DNA damage shapes extracellular growth factor responses through AKT phosphorylation dynamics to control virus latency

“…By directly linking perturbations in AKT phosphorylation dynamics and subcellular localization to defects in downstream mTORC1 signaling, our findings support the possibility that AKT shuttles between nuclear and cytoplasmic compartments and thereby carrying a nuclear signal (via phosphorylation) back out to the cytoplasm (inside-out signaling) to phosphorylate its downstream targets (model, Figure 7). This starkly contrasts with the typical direction of cell signaling from the cell membrane or endosomes via receptor tyrosine kinases to the nucleus to activate transcription factors, such as CREB or FOXO (Cox et al, 2008;Manning and Toker, 2017;Terenzio et al, 2017). This is reminiscent of activation of NFkB transcription factor family members resident in the cytoplasm by the nuclear DNA damage response signaling (Huang et al, 2003;McCool and Miyamoto, 2012;Wu et al, 2006).…”

hnRNPs Interacting with mRNA Localization Motifs Define AxoNAl RNA Regulons

“…These locally generated proteins contribute to growth and function of axons as well as retrograde signaling for injury responses and survival in the peripheral nervous system (PNS) (2,3). The transport of mRNAs into axons and their translation within axons can be regulated by extracellular stimuli (4).…”

Microglia monitor and protect neuronal function via specialized somatic purinergic junctions

“…To date, the majority of studies have focused on the interactions between microglial processes and synaptic elements, including axonal boutons and dendritic spines, which have been commonly perceived as the main form of interaction between microglia and neurons (8,9). However, neurons are extremely polarized cells with a high degree of functional independence concerning metabolism and signal integration in their dendritic and axonal compartments (10)(11)(12). In line with this, the large-scale structure of neurons (i.e.…”