ER Proteostasis Control of Neuronal Physiology and Synaptic Function

Neuronal proteostasis is maintained by the dynamic integration of different processes that regulate the synthesis, folding, quality control, and localization of proteins. The endoplasmic reticulum (ER) serves as a fundamental pillar of the proteostasis network, and is emerging as a key compartment to sustain normal brain function. The unfolded protein response (UPR), the main mechanism that copes with ER stress, plays a central role in the quality control of many ion channels and receptors, in addition to crosstalk with signaling pathways that regulate connectivity, synapse formation, and neuronal plasticity. We provide here an overview of recent advances in the involvement of the UPR in maintaining neuronal proteostasis, and discuss its emerging role in brain development, neuronal physiology, and behavior, as well as the implications for neurodegenerative diseases involving cognitive decline.