THE HUMAN PROTEIN ATLAS BLOG

Image of the week - Endoplasmic reticulum

2016-09-02
Endoplasmic reticulum Image of the week Subcell Atlas


Staining of Calnexin (green) with DNA (blue) in A-431 cells

Welcome back blog fans! After a brief hiatus the image of the week highlights from the HPA are back! This week we are discussing the Endoplasmic reticulum, which is not just difficult to say, but is where many of your proteins are made.

The endoplasmic reticulum (ER) is one of the largest organelles in the cell. It is a delicate membranous network composed of sheets and tubules that spreads throughout the whole cytoplasm and is actually contiguous to the nuclear membrane. Two major forms of the ER can be distinguished: the rough ER and the smooth ER. Both have different functions. The rough ER is covered by ribosomes that make most of the transmembrane and secreted proteins, while the smooth ER, devoid of ribosomes, is mainly dedicated to the synthesis of lipids and other biomolecules.

The rough ER got its name from its appearance under the electron microscope. The ER membrane is covered densely by ribosomes, which made it look ?rough? compared to other membranes in the cells. Ribosomes are the cellular machines that translate the genetic code into a protein. All translations (RNA to protein) are initiated in the cytoplasm, but a signal peptide guides the ribosome together with the nascent protein to the ER where the translation continues. Here, the newly translated proteins get in contact with a dense meshwork of ER-resident proteins. One example for an ER-resident protein, Calnexin is shown in Figure 1 in A-431 epidermal carcinoma cells. Calnexin belongs to a group of proteins that are called chaperons. Like human chaperones that supervise the correct behavior of young people, protein chaperones such as calnexin ensure the correct folding of a young proteins (David et al, 1993).

Unfolded or misfolded proteins can cause ER stress by accumulating in the lumen (inside the ER). This process activates the unfolded protein response (UPR), which resolves the stress by reducing the overall protein synthesis, increasing the capacity for protein folding, and the removing misfolded proteins by the ER-associated degradation (ERAD) (Travers et al, 2000). If the stress is not alleviated however, it ultimately induces cell death known as apoptosis. Several pathological processes, especially neurological diseases (Roussel et al, 2013), are linked to ER stress as well as contributing to an imbalance in the UPR, causing diseases such as Parkinson's (Omura et al, 2013 ) or Alzheimer's (Fonseca et al, 2013).

The smooth ER harbors a wide range of enzymes to catalyze a plethora of reactions. Most important is the synthesis of lipids. They are required for the building of new membranes or hormones (Fagone & Jackowski, 2008). The ER is also one of the organelles that interacts a lot with other organelles. Not only does it give rise to two other vesicle-like organelles (peroxisomes and lipid droplets), but also the Golgi apparatus depends on a constant influx from the ER to keep up its structure. Additionally, the ER forms special contact sites with many organelles such as the mitochondria and plasma membrane, where lipids and ions are exchanged (Helle et al, 2013).

We would like to thank all the members of the Subcellular Human Protein Atlas who generate these images and especially to Peter Thul for contributing this article about the endoplasmic reticulum.