Lipid-Modifying Enzyme: New Target for Pan-Viral Therapeutics

ScienceDaily (Dec. 7, 2011) Three different disease-causing viruses -poliovirus, coxsackievirus, and hepatitis C -- rely on their unwilling host for the membrane platforms enriched in a specific lipid, phosphatidylinositol 4 phosphate (PI4P) on which they can replicate, Rutgers University researchers said on Dec. 7, at the American Society for Cell Biology annual meeting in Denver.
The viruses carry proteins that enable them to gain access to the P14P lipid for replication. The proteins snare one of the host's own lipid-modifying enzymes, a Type III PI4-kinase (PI4-kinase), reported Nihal Altan-Bonnet, Ph.D., of Rutgers University. The PI4-kinase may prove to be an excellent target for panviral therapeutics, Altan-Bonnet said. When the Rutgers researchers blocked this PI4-kinase, the invading viruses all ceased replicating, and their host cells survived. The Rutgers group has extended its investigations to identify other viruses that might be vulnerable to this countermeasure. Blocking the PI4-kinase was effective, Altan-Bonnet explained, because invading viruses require this enzyme to manufacture the P14P lipid for the platforms that they must set up on the host's membrane-bound organelles, which include the Golgi apparatus and the mitochondria. The viruses can replicate only on cell membrane platforms enriched with the P14P lipid. To gain access to the lipid, the viruses employ a protein that hijacks the cell's P14-kinase. They then use it to generate the lipid that enriches the platform. Once established, the viruses rapidly make copies of themselves that go on to infect other cells in the organism. In normal, uninfected cells, the level of PI4P lipid on organelle membranes is generally low and increases only when signaling and membrane-remodeling proteins are required by the cell, said Altan-Bonnet. But in infected cells, levels of PI4P lipid dramatically increase, reflecting the viruses' need for more PI4P lipid-enriched membrane surface to anchor their replication machinery. Altan-Bonnet's lab also found that these membrane surfaces are enriched with cholesterol as well as PI4P lipid. Normally, cholesterol regulates membrane fluidity and elasticity, generating domains to sequester proteins so they can interact effectively. Altan-Bonnet said that the PI4P lipid and cholesterol together may generate "sticky" membrane domains that viruses exploit for replication. Since viral proteins are relatively few after they invade the host cell, a "sticky" rallying point could be critical to their survival. The researchers also discovered that RNA polymerases, which are vital for synthesizing the nucleic acids of viruses, have specific binding sites that lock onto PI4P lipids.

Reference: http://www.sciencedaily.com/

Discovery On How Sugars Are Moved Throughout a Plant

ScienceDaily (Dec. 8, 2011) Food prices are soaring at the same time as Earth's population is nearing 9 billion. As a result the need for increased crop yields is extremely important. New research led by Carnegie's Wolf Frommer into the system by which sugars are moved throughout a plant -- from the leaves to the harvested portions and elsewhere -- could be crucial for addressing this problem. Their work is published December 8 by Science Express.
Just as it's necessary for the human body to move nutrients to all of the organs, it is vital for green plants to transport sugars to supply its various parts. In humans, this is the circulatory system's job. But plants do not have a heart-like pump to move these vital energy sources. Instead, plants use a molecular pump. Twenty years ago, the Frommer team identified one of the key components of this molecular pump, which actively loads a sugar called sucrose into the plant's veins, a tissue called phloem. But how the sucrose produced in the leaves via photosynthesis is delivered to the transporters that move it into the phloem has remained a mystery. Thus, a critical piece of the molecular pump was unknown--the protein that moves the sucrose to the inside of the plant's leaf cell walls. Frommer's team included Carnegie's Li-Qing Chen, the paper's lead author, Xiao-Quing Qu, Bi-Huei Hou and Davide Sosso, as well as Sonia Osorio and Alisdair Fernie of the Max Planck Institute of Molecular Plant Physiology. In this new research they have identified the missing piece of the molecular pump system. "Like engineers, we can now fine tune the pump components to address one of the major challenges for our future -- namely, to increase the translocation of sugars towards seeds in order to increase crop yield," Frommer said "The identification of these critical transporters is a major step towards developing strategies to ensure food supplies and keep food prices in check." What's more, pests are abusing these transporters and using them to gain access to the plants sucrose pools. The identification of the role of these transporters in plant infections provides a new perspective on plant pathology and a totally new way of protecting pants from pathogens, further increasing crop yields and food security. The identification of the function of this missing piece of the molecular pump involved in transporting sugar in plant makes it highly likely that the animal-cell version of this same protein fulfills a similar role in animals and humans. This would be a major breakthrough for diabetes and obesity research, since a yet unidentified transporter protein is responsible for essential steps in the movement of sugars from the intestine into the blood as well as for efflux from liver cells for maintenance of blood glucose levels

A 'Wild Card' in Your Genes

ScienceDaily (Dec. 7, 2011) The human genome and the endowments of genes in other animals and plants are like a deck of poker cards containing a "wild card" that in a genetic sense introduces an element of variety and surprise that has a key role in life. That's what scientists are describing in a review of more than 100 studies on the topic that appears inACS Chemical Biology.
Rahul Kohli and colleagues focus on cytosine, one of the four chemical "bases" that comprise the alphabet that the genetic material DNA uses to spell out everything from hair and eye color to risk of certain diseases. But far from just storing information, cytosine has acquired a number of other functions that give it a claim to being the genome's wild card. "In poker, the rules of the game can occasionally change," they note in the article. "Adding a 'wild card' to the mix introduces a new degree of variety and presents opportunities for a skilled player to steal the pot. Given that evolution is governed by the same principles of risk and reward that are common to a poker game, it is perhaps not surprising that a genomic 'wild card' has an integral role in biology." They discuss the many faces of cytosine that make it such a game-changer and the biological processes that help to change its identity. Removing something called an amine group from cytosine, for instance, allows the immune system to recognize and destroy foreign invaders such as viruses. Adding so-called "methyl groups" on cytosines acts as on/off switches for genes. The authors say that these many faces of cytosine allow it to play various roles and give it true "wild card" status.