In 2013, scientists linked a cellular response called the unfolded protein response (UPR) to a series of neurodegenerative diseases, including such major health issues as Parkinson’s and Alzheimer’s Disease. According to their work, the unfolded protein response is a reduction in translation as a result of a series of enzymes that modify a translation initiation factor, eIF2, as below:

In the above sequence, the unfolded protein sensor binds to unfolded protein, such as the pathogenic amyloid-beta found in the brains of Alzheimer’s Disease patients. This sensor then phosphorylates PERK, or protein kinase RNA-like endoplasmic reticulum kinase. This leads to downstream effects on eIF2, inhibition of which represses translation. It is thought that symptoms of neurodegenerative disease may be a result of this reduced translation.

Regarding unfolded proteins discussed in the passage, which organelle is likely to be the site of initial protein folding in normal cells?

There are two models for the operation of the Golgi apparatus in eukaryotic cells. As it is difficult to visualize the operation of cells at the molecular level in real time, scientists typically rely on static electron micrographs to see the morphology of organelles. As a result, the dynamic operation of these organelles can sometimes be unclear.

Cisternal Maturation Hypothesis

In the cisternal maturation hypothesis, the cisternae of the Golgi apparatus evolve. Proteins leave the endoplasmic reticulum, and enter the cis-Golgi. The cisterna of the cis-Golgi then matures, with its enzymatic contents and internal environment changing as it becomes the medial-Golgi, and, eventually, the trans-Golgi.

In this model, the proteins never physically leave their membrane-bound cisternae during their transit across the Golgi. Instead, the entire unit of contents remains within the evolving cisternae.

Vesicular Transport Hypothesis

In contrast to the cisternal maturation hypothesis, the vesicular transport hypothesis posits that the cis-, medial-, and trans-Golgi cisternae are more static structures. Instead of evolving around their contents, the contents are physically shuttled via vesicular intermediates from each cisterna to the next.

In the case of vesicular transport, vesicles are shuttled along microtubules. Motor proteins facilitate this movement, with unique proteins being used for each direction of movement along a microtubule.

Which of the following is most likely to take place in the Golgi apparatus?

Scientists use a process called Flourescent In-Situ Hybridization, or FISH, to study genetic disorders in humans. FISH is a technique that uses spectrographic analysis to determine the presence or absence, as well as the relative abundance, of genetic material in human cells.

To use FISH, scientists apply fluorescently-labeled bits of DNA of a known color, called probes, to samples of test DNA. These probes anneal to the sample DNA, and scientists can read the colors that result using laboratory equipment. One common use of FISH is to determine the presence of extra DNA in conditions of aneuploidy, a state in which a human cell has an abnormal number of chromosomes. Chromosomes are collections of DNA, the totality of which makes up a cell’s genome. Another typical use is in the study of cancer cells, where scientists use FISH labels to ascertain if genes have moved inappropriately in a cell’s genome.

Using red fluorescent tags, scientists label probe DNA for a gene known to be expressed more heavily in cancer cells than normal cells. They then label a probe for an immediately adjacent DNA sequence with a green fluorescent tag. Both probes are then added to three dishes, shown below. In dish 1 human bladder cells are incubated with the probes, in dish 2 human epithelial cells are incubated, and in dish 3 known non-cancerous cells are used. The relative luminescence observed in regions of interest in all dishes is shown below.

A scientist discovers that there is a class of proteins called tumor suppressors. These proteins are present in the cytosol of almost all human cells, and serve to downregulate cell division by preventing entry into key parts of the cell cycle. Where are these proteins most likely synthesized?

There are two models for the operation of the Golgi apparatus in eukaryotic cells. As it is difficult to visualize the operation of cells at the molecular level in real time, scientists typically rely on static electron micrographs to see the morphology of organelles. As a result, the dynamic operation of these organelles can sometimes be unclear.

Cisternal Maturation Hypothesis

In the cisternal maturation hypothesis, the cisternae of the Golgi apparatus evolve. Proteins leave the endoplasmic reticulum, and enter the cis-Golgi. The cisterna of the cis-Golgi then matures, with its enzymatic contents and internal environment changing as it becomes the medial-Golgi, and, eventually, the trans-Golgi.

In this model, the proteins never physically leave their membrane-bound cisternae during their transit across the Golgi. Instead, the entire unit of contents remains within the evolving cisternae.

Vesicular Transport Hypothesis

In contrast to the cisternal maturation hypothesis, the vesicular transport hypothesis posits that the cis-, medial-, and trans-Golgi cisternae are more static structures. Instead of evolving around their contents, the contents are physically shuttled via vesicular intermediates from each cisterna to the next.

In the case of vesicular transport, vesicles are shuttled along microtubules. Motor proteins facilitate this movement, with unique proteins being used for each direction of movement along a microtubule.

In the cisternal maturation hypothesis, a change in which of the following is most likely to change the charge of the carboxyl and amino termini in a protein moving through the Golgi network?

In eukaryotic cells, what organelle is associated with translation of antibody proteins?

Scientists identify a mutation in an isolated community in central Africa that prevents individuals from detoxifying potentially harmful organic molecules, leading to a high percentage of people who become very ill after consuming alcohol. What cellular organelle does this mutation most likely affect the most?

The liver is one of the major sites for drug metabolism and detoxification. Which organelle would you expect to play an important role in this process?

Which of the following organelles is most important in testosterone synthesis?

Type 1 diabetes is a well-understood autoimmune disease. Autoimmune diseases result from an immune system-mediated attack on one’s own body tissues. In normal development, an organ called the thymus introduces immune cells to the body’s normal proteins. This process is called negative selection, as those immune cells that recognize normal proteins are deleted. If cells evade this process, those that recognize normal proteins enter into circulation, where they can attack body tissues. The thymus is also important for activating T-cells that recognize foreign proteins.

As the figure below shows, immune cells typically originate in the bone marrow. Some immune cells, called T-cells, then go to the thymus for negative selection. Those that survive negative selection, enter into general circulation to fight infection. Other cells, called B-cells, directly enter general circulation from the bone marrow. It is a breakdown in this carefully orchestrated process that leads to autoimmune disease, such as type 1 diabetes.

T-cells use receptors in their activity to defend their biological hosts. These receptors are protein molecules, heavily modified before being sent to the cell's surface. In which organelle does the majority of such modification take place?

Which of the following choices describe functions of the Golgi apparatus?

I. Post-translational modifications

II. Formation of lysosomes

III. Carbohydrate synthesis

IV. Protein trafficking