Vesicles: membrane-bound organelle intermediates

The endomembrane system is perhaps the easiest way to identify a eukaryotic cell. It is composed of the various membranes that surround the organelles including the nuclear envelope, the endoplasmic reticulum (ER),  the Golgi bodies, the lysosomes (in animals), the vacuoles (in plants), endosomes and the plasma membrane.

This GIF, found on the Brooklyn Cuny Website, illustrates the pathways of proteins through the endomembrane system from the nuclear membrane (at the bottom-most part of the ER) to the lysosome or the plasma membrane. Proteins are stored in the lysosome or moved into the extracellular place. Note that transport vesicles link the larger organelles and carry proteins between them. 

Artemisa Garnica, a senior zoology major at CSU, explained that scientists study the endomembrane system to understand how and why proteins go to their respective locations. In this, we might be able to understand secretory diseases in both humans and animals, including some forms of cancer. 

Discovering Sec(retory) Mutants: The Genetics Behind Vesicles

On March 28, Randy Schekman, a 2013 Nobel Prize winner, gave a lecture in CSU's Lory Student Theater on "Genes and proteins that organize secretion and autophagy." Until the last 30 years, the mechanisms of the endomembrane transport system were largely unknown.

 Schekman and his lab were responsible for identifying secretory defects and looking for their genetic basis. One of the genes they related to a defect  became known as yeast cell gene Sec1 (labeled after its secretory mutation), according to Scheckman.  The Sec1 mutation disallowed membrane fusing between the vesicle and the plasma membrane so that the vesicles accumulated just inside the membrane.

His lab went on to identify several genes with secretory mutations, defects in vesicle budding, formation, and fusion.

In the lecture, he also explained that several human diseases occur due to secretory defects, including anemia and a rare condition that leads to incomplete formation of the skull.

The Mechanism
Schekman's lab also headed research on COPII, a coat protein that coats the vesicles.

According to Marinus Pilon, a Cell Biology professor at CSU who worked with Schekman, COP II is catalyzed to bind Sar during vesicle budding.

This image, found on the nature website shows vesicle budding, when a vesicle forms on the surface of the ER. The outer proteins (Sec23) bind to Sar  along with other proteins and form vesicles, which allow the stable transport of protein products through the cytoplasm.

These mechanisms provide possible points of investigation for diseases, especially if they result in the build-up of certain secreted proteins.

The exosome as a transporter of diseases and treatments

This infographic, found on The Scientist website, shows a basic understanding of exosomes, which carry proteins outside of the cell. Click the link to see it larger.

General

Exosomes were once thought to discard waste outside the cell. 7th Space Interactive, however, just published an article saying that according to some studies in the Journal of Neuroinflammation, exosomes also transfer proteins between cells.

This concept is not entirely new, as a 2011 article published on The Scientist called "Exosome Explosion" looks at the exosome as a cell signal transmitter that carries not just proteins, but protein precursors (like mRNA).

Disease Carriers

Exosomes have been found to carry infected material between cells, contributing to the growth of cancer, as explained in this article from PubMed. Additionally, exosomes may export therapeutic drugs, inhibiting their effectiveness.

The article from 7th Space Interactive also says that, in neurological pathways, the build up of neurotoxins may cause cellular damage and may contribute to Alzheimer's, Parkinson's and other neurological diseases. 

Treatments

A study done by the Department of Physiology, Anatomy, and Genetics at the University of Oxford looked at synthetic exosome delivery of drugs as a possible route for treatment of neurodiseases, according to Molecular Therapy.  The exosomes could possibly carry tumor inhibitors, as stated in the article:

Zhuang et al.1 build on previous findings by the same researchers that T-cell-derived exosomes are preferentially taken up by immature myeloid cells such as macrophages and microglial cells.10 Given the selective uptake of exosomes by macrophages, already demonstrated by these authors, and the newly established properties of exosomes as drug delivery vehicles,8 Zhuang and colleagues investigated whether T-cell-derived exosomes could be used to deliver anti-inflammatory agents specifically to microglial cells in the brain. They used a noninvasive intranasal route to bypass the BBB. Unloaded exosomes derived from a variety of mouse cell lines and labeled with a biological dye were first administered intranasally 2 µg at a time over a 10-minute period. Labeled exosomes were detected in the olfactory bulb within 30 minutes and up to 24 hours after administration. Multiorgan imaging demonstrated their selective homing to the brain and, to a lesser extent, the intestine. These initial experiments with unloaded exosomes demonstrated their fast and selective homing to the brain after intranasal administration.

Understanding of organelle changes treatment approach to jellyfish stings

Photo: Wikipedia.

According to The Australian "Higher Education," scientists from James Cook University and Cairns Hospital claim that vinegar should not be used to treat jelly fish stings.

This short video (embedding was disabled) talks about the mechanism for a jellyfish sting. Generally speaking, an electric pulse through the tentacles triggers a reaction in the cnidoblasts, the stinging cell. The nematocyst, an organelle in the cnidoblasts is  harpooned into the prey, and the nematocysts release neurotoxins into the organism.

This diagram, found on the Kennesaw State University website, shows the nematocyst in the cnidoblast before and after discharge.

When scientists initially recommended vinegar for jelly fish sting treatment, they  based their recommendation on the discovery that vinegar reduces the ability of inactive nematocysts to activate. However, according to Higher Education, the research groups involved in this newly published study discovered higher levels of toxicity in patients treated with vinegar because the vinegar made the already discharged nemacysts discharge more venom.

Lysosomal degradation of ferritin found crucial to iron homeostasis

A study published by the Harvard Medical School, Dana-Farber Cancer Institute and Beth Israel Deaconess Medical Center demonstrated a lysosome-dependent mechanism for iron storage and release in cells, according to medicalxpress.com .

Although cells need iron, especially red blood cells that depend on iron (II) to carry oxygen, too much iron free radicals lose in the cells can cause iron overload that transfers to and damages organs. A more complete analysis of iron-related health concerns can be found  in Jane Brody's New York Times health blog article published in 2012, "A Host of Ills When Iron’s Out of Balance."

The basic science behind the maintenance of iron levels can be traced to ferritin, a protein that surrounds unused iron ions and stores them. 

This diagram, retrieved on April 2nd from the Memorial University of Newfoundland Website shows the production of the ferritin, which is regulated by an iron-activated regulator protein. In the picture on the left (a), the active IRE binding protein is blocking the expression of the iron response element. In the picture on the right (b), when iron levels are high, iron binds to the active IRE binding protein, changing it's shape and causing it to detach from the mRNA. The mRNA that follows it, the ferritin encoding sequence, is then expressed in order to bind and store the iron.

However, the new study published in Nature looks at the next stage, after expression of the ferritin protein, when iron levels decrease. After someone has been seriously injured, given blood, or even menstruated, iron levels can become low. The cell then requires a mechanism to retrieve iron from the ferritin protein.

The study suggests that phagocytosis occurs as the lysosome digests the ferritin protein to release the iron contained within its cage-like structure. The scientists also found the cargo carrier that constitutes the ferritin's specific pathway of ferritin to lysosomal degradation.

Read Elizabeth Cooney's medicalxpress article for more information. Additionally, the abstract and images are available from nature.com.
 

Researchers at the Pacific Northwest Research laboratory develop action based probe technique

According to an article published Monday on Phys.org, researchers at the Pacific Northwest Research Laboratory developed a new tool called an action based probe (ABP) that allows scientists to see processes occurring in living cells.

This image is from the primary article available at Wiley.com from the journal Angewandte Chemie (International Edition) and shows the movement of the enzymes within the cell. 

The technique allows fluorescent tags to enter the lysosome and trace only active forms of the cathepsins, a group of cysteine proteases (cysteine-cutting enzymes). Cysteine is an amino acid with a terminal sulfur hydryl (sulfur and hydrogen) group, and proteases digest proteins and their components for recycling in the cell. Thus, if the cathepsins malfunction, a cell cannot digest proteins containing cysteine.

In the particular case of studying cathepsins, this technique can be used to analyze certain types of cancer associated with the malfunction of this family of enzymes.

This new technique has several other applications, especially if active enzyme-specific tags can be developed for a series of enzymes that cause other diseases and symptoms. It will allow scientists to see not just when enzymes are present and working, but also detect when they are lacking or malfunctioning.

According to Phys.org, researchers at Harvard's Wyss Institute have built self-assembling nanocages comprised of DNA. 

This image, found with the article on Phys.org, shows the DNA 3-D figures the scientists have made and imaged with the PAINT DNA technique. Each structure is composed of DNA tripods that attach end-to-end, forming polygons.

The researchers hope to use this for several medical applications, such as highly localized drug administration with metal coating, but currently are working to ensure the stability of the structures and the DNA. Although DNA is a fairly stable molecule in itself, common enzymes and components of the extra-cellular matrix easily disassemble the DNA.

The rightmost cage shown above, the biggest created to date, is about 1-tenth the size of a bacteria cell.

The Abstract for the research, published in Science Magazine, can be found here.

Researchers at MIT work to create nanobiotic plants inserting modified nanotubes into chloroplasts

According to Business Standard, a research team led by Michael Strano at MIT is working to produce plants that can sense pollution, explosives, and chemical weapons. The team might also try to incorporate electronics into plants.

The mechanisms the teams are using, such as those used to sense pollutants like nitric oxide, requires inserting modified nanotubes into functional parts of the plant, such as the chloroplast.

This image, found on Guardian Liberty Voice, illustrates how fluorescence can be seen in plants. This particular part of the experiment showed a 30% increase in the plants' ability to harvest energy from sunlight.

The first step with each new detection ability is to synthesize nanotubules with sensory ability. These tubes have a fluorescent pigment in them that changes when the target molecule (such as a pollutant) binds to the receptors.

The original article about the photonic chemical sensors in vivo and ex vivo, authored by Giraldo, was published in Nature Materials earlier this month.

This study suggests that plants may be a more reliable detector for small levels of pollutants than man-made detectors.