How Different Forms of the Endoplasmic Reticulum Affect the Brain

Sree, S., Parkkinen, I., Their, A., Airavaara, M., & Jokitalo, E. (2021). Morphological Heterogeneity of the Endoplasmic Reticulum within Neurons and Its Implications in Neurodegeneration. Cells, 10(5), 970. https://doi.org/10.3390/cells10050970

Cells, the basic building blocks of life, may have another “cell” within them: the endoplasmic reticulum (ER). Out of the many organelles - specialized subunits that have a specific function - within the cell, the ER is one of the most important. Its functions are split between the rough ER and the smooth ER - named based on the presence/absence of the protein producing ribosomes on the ER’s surface - where the rough ER is the site of protein synthesis as a result of bound ribosomes while the smooth ER stores lipids and steroids.

It is often considered to be the “cell within the cell” primarily in neurons, brain cells that help process information, due to its tendency to branch out extensively across the receiving and transmitting ends. This spread allows the ER to be actively involved in almost every cellular process, with their shape varying based on their location within the neuron and the pathway they are involved in. As a result, the shape of the ER plays a central role in many neurodegenerative disorders.

The neuron is composed of 3 main regions: the soma, the dendrites, and the axon. The soma is the site of the cell’s nucleus as well as the majority of organelles. Within the soma, the ER is highly compacted to allow for a higher surface area-to-volume ratio that allows for greater organelle activity. This also provides a larger space for ribosome attachment, as most of the ER within the soma are rough. Due to the stacked nature of the ER, they were named as Nissl bodies after the scientist Franz Nissl who discovered their masses in the 19th century. This version of the ER differs from normal ones as it has a more complex structure involving larger tubules and greater ribbon-like folds.

The dendrites, long spindle fibers attached to the soma, help with receiving information sent by other neurons. Dendritic ER tends to be narrow yet extremely complex in shape for an increased capacity for protein synthesis when receiving signals from other neurons. Dendritic ER are usually divided into two separate groups: proximal and distal somatodendritic ER. This just differentiates between how close the ER is to the soma. While proximal, or close, somatodendritic ER tend to be high in ribosome content, the distal, or far, somatodendritic ER are usually free of ribosomes excluding the occasional clusters. In general terms of function, dendritic ER are spread in a wide network to assist in the composition of the cell’s membrane and the provision of a pathway for proteins and other small molecules to reach locations within the cell.

At the axon, or the long “tail” of the neuron where impulses are carried off to other neurons, rough ER is sparse at the axon terminal, despite the presence of ribosomes. Smooth ER is more common, appearing in dense stacks at the initial ends of axons. Even among axons, ER's structure varies, with a positive relationship formulated between axon size and the number of ER tubules that help guide intracellular materials. One research study found that extremely narrow ER tubules were especially abundant within the axon, allowing for quicker particle transportation.

Due to the importance of the ER in the neuron and the shape/structure variation, there are a variety of neurodegenerative diseases associated with the ER. In fact, many neurodegenerative disorders are also called protein misfolding disorders due to the nature of protein mutation that results in neurodegeneration. For example, misfolding of alpha-synuclein, a protein involved in the neuron’s synapses, can increase the risk of Parkinson’s disease. Some disorders can be brought upon by altered ER structure, with previous papers attributing this variation to the prognosis of Alzheimer’s disease and hereditary spastic paraplegias (HSP). Thus, the consequences of ER defects need to be thoroughly investigated in order to better understand neurological disorders and create potential treatment options.

Works Cited:

Kuijpers M, Nguyen PT, Haucke V. The Endoplasmic Reticulum and Its Contacts: Emerging Roles in Axon Development, Neurotransmission, and Degeneration. The Neuroscientist. 2023;0(0). doi:10.1177/10738584231162810