The endomembrane system (endo = “within”) is a group of membranes and organelles (Figure 1) in eukaryotic cells that works together to modify, package, and transport lipids and proteins. It includes the nuclear envelope, lysosomes, vesicles, and the endoplasmic reticulum and Golgi apparatus, which we will cover shortly. Although not technically within the cell, the plasma membrane is included in the endomembrane system because, as you will see, it interacts with the other endomembranous organelles. The endomembrane system does not include the membranes of either mitochondria or chloroplasts.
Figure 1 illustrates the connections of the endomembrane system as a (green) integral membrane protein in the ER is modified by attachment of a (purple) carbohydrate. Vesicles with the integral protein bud from the ER and fuse with the cis face of the Golgi apparatus. As the protein passes along the Golgi’s cisternae, it is further modified by the addition of more carbohydrates. After its synthesis is complete, it exits as integral membrane protein of the vesicle that bud from the Golgi’s trans face and when the vesicle fuses with the cell membrane the protein becomes integral portion of that cell membrane.
The endoplasmic reticulum (ER) (Figure 1) is a series of interconnected membranous sacs and tubules that collectively modifies proteins and synthesizes lipids. However, these two functions are performed in separate areas of the ER: the rough ER and the smooth ER, respectively.
The hollow portion of the ER tubules is called the lumen or cisternal space. The membrane of the ER, which is a phospholipid bilayer embedded with proteins, is continuous with the nuclear envelope.
The rough endoplasmic reticulum (RER) is so named because the ribosomes attached to its cytoplasmic surface give it a studded appearance when viewed through an electron microscope (Figure 2).
Ribosomes transfer their newly synthesized proteins into the lumen of the RER where they undergo structural modifications, such as folding or the acquisition of side chains. These modified proteins will be incorporated into cellular membranes—the membrane of the ER or those of other organelles—or secreted from the cell (such as protein hormones or enzymes). The RER also makes phospholipids for cellular membranes.
If the phospholipids or modified proteins are not destined to stay in the RER, they will reach their destinations via transport vesicles that bud from the RER’s membrane (Figure 1).
Since the RER is engaged in modifying proteins (such as enzymes, for example) that will be secreted from the cell, you would be correct in assuming that the RER is abundant in cells that secrete proteins. This is the case with cells of the liver, for example.
The smooth endoplasmic reticulum (SER) is continuous with the RER but has few or no ribosomes on its cytoplasmic surface. Functions of the SER include synthesis of carbohydrates, lipids, and steroid hormones; detoxification of medications and poisons; and storage of calcium ions.
In muscle cells, a specialized SER called the sarcoplasmic reticulum is responsible for storage of the calcium ions that are needed to trigger the coordinated contractions of the muscle cells.
Heart disease is the leading cause of death in the United States. This is primarily due to our sedentary lifestyle and our high trans-fat diets.
Heart failure is just one of many disabling heart conditions. Heart failure does not mean that the heart has stopped working. Rather, it means that the heart can’t pump with sufficient force to transport oxygenated blood to all the vital organs. Left untreated, heart failure can lead to kidney failure and failure of other organs.
The wall of the heart is composed of cardiac muscle tissue. Heart failure occurs when the endoplasmic reticula of cardiac muscle cells do not function properly. As a result, an insufficient number of calcium ions are available to trigger a sufficient contractile force.
Cardiologists (cardi = “heart”; ologist = “one who studies”) are doctors who specialize in treating heart diseases, including heart failure. Cardiologists can make a diagnosis of heart failure via physical examination, results from an electrocardiogram (ECG, a test that measures the electrical activity of the heart), a chest X-ray to see whether the heart is enlarged, and other tests. If heart failure is diagnosed, the cardiologist will typically prescribe appropriate medications and recommend a reduction in table salt intake and a supervised exercise program.
We have already mentioned that vesicles can bud from the ER and transport their contents elsewhere, but where do the vesicles go? Before reaching their final destination, the lipids or proteins within the transport vesicles still need to be sorted, packaged, and tagged so that they wind up in the right place. Sorting, tagging, packaging, and distribution of lipids and proteins takes place in the Golgi apparatus (also called the Golgi body), a series of flattened membranes (Figure 3).
The receiving side of the Golgi apparatus is called the cis face. The opposite side is called the trans face. The transport vesicles that formed from the ER travel to the cis face, fuse with it, and empty their contents into the lumen of the Golgi apparatus. As the proteins and lipids travel through the Golgi, they undergo further modifications that allow them to be sorted. The most frequent modification is the addition of short chains of sugar molecules. These newly modified proteins and lipids are then tagged with phosphate groups or other small molecules so that they can be routed to their proper destinations.
Finally, the modified and tagged proteins are packaged into secretory vesicles that bud from the trans face of the Golgi. While some of these vesicles deposit their contents into other parts of the cell where they will be used, other secretory vesicles fuse with the plasma membrane and release their contents outside the cell.
In another example of form following function, cells that engage in a great deal of secretory activity (such as cells of the salivary glands that secrete digestive enzymes or cells of the immune system that secrete antibodies) have an abundance of Golgi.
In plant cells, the Golgi apparatus has the additional role of synthesizing polysaccharides, some of which are incorporated into the cell wall and some of which are used in other parts of the cell.
Many diseases arise from genetic mutations that prevent the synthesis of critical proteins. One such disease is Lowe disease (also called oculocerebrorenal syndrome, because it affects the eyes, brain, and kidneys). In Lowe disease, there is a deficiency in an enzyme localized to the Golgi apparatus. Children with Lowe disease are born with cataracts, typically develop kidney disease after the first year of life, and may have impaired mental abilities.
Lowe disease is a genetic disease caused by a mutation on the X chromosome. The X chromosome is one of the two human sex chromosome, as these chromosomes determine a person’s sex. Females possess two X chromosomes while males possess one X and one Y chromosome. In females, the genes on only one of the two X chromosomes are expressed. Therefore, females who carry the Lowe disease gene on one of their X chromosomes have a 50/50 chance of having the disease. However, males only have one X chromosome and the genes on this chromosome are always expressed. Therefore, males will always have Lowe disease if their X chromosome carries the Lowe disease gene. The location of the mutated gene, as well as the locations of many other mutations that cause genetic diseases, has now been identified. Through prenatal testing, a woman can find out if the fetus she is carrying may be afflicted with one of several genetic diseases.
Geneticists analyze the results of prenatal genetic tests and may counsel pregnant women on available options. They may also conduct genetic research that leads to new drugs or foods, or perform DNA analyses that are used in forensic investigations.