February 6, 2009

Aliquots — research highlights from VMC laboratories

We welcome suggestions for research to highlight in Aliquots. The items should be primary research articles (no reviews, editorials or commentaries) published within the last two months in a peer-reviewed journal. Please send the article citation (PDF if available) and any other feedback about the column to: aliquots@vanderbilt.edu.


Reovirus JAMs into bloodstream

Reoviruses infect the intestine and spread systemically to the central nervous system. They offer an ideal experimental system for studying how viruses interact with their hosts at different steps in the disease process.

Annie Antar, Ph.D., Jenn Konopka, Ph.D., Terence Dermody, M.D., and colleagues used mice lacking expression of the reovirus receptor JAM-A to define the function of JAM-A in reovirus disease. They report in the Jan. 22 issue of Cell Host & Microbe that JAM-A is not essential for viral replication in the intestine after oral inoculation or in the brain after intracranial inoculation. However, JAM-A is required for infection of primary endothelial cells (that line blood vessels), establishment of a bloodstream infection, and spread from the intestines.

Their finding that a broadly expressed receptor mediates a specific aspect of viral pathogenesis suggests that virus-host interactions require multiple receptors for each step of the disease process and has important implications for antiviral strategies.

Leigh MacMillan


Self-promoting tumor signals

Inflammation plays many roles in cancer development, and inflammatory cells within tumors modulate tumor growth, invasion, metastasis and the growth of blood vessels that “feed” the tumor (angiogenesis).

Recently, inflammatory (myeloid) cells that also have characteristics of blood vessel lining cells have been identified in some tumors and shown to promote tumor growth and angiogenesis. But the chemical signals that incite the development of these tumor-promoting cells has not been clear.

In the Jan. 1 issue of Cancer Research, Pampee Young, M.D., Ph.D., and colleagues show that a chemical cue – called tumor necrosis factor alpha (TNFa) – produced at chronic, low levels by the tumors themselves induces the inflammatory cells to take on this dual identity. These cells promoted tumor growth and angiogenesis in mouse models of melanoma, lung cancer and breast cancer, the researchers found.

Since TNFa inhibitors are already available to treat inflammatory disorders like arthritis, characterizing TNFa’s role in tumor-myeloid cell interactions could aid in the development of new cancer therapies using TNFa-inhibitors.

Melissa Marino


No poles, no DNA division

During development and throughout life, cells cycle – they replicate their DNA and divide it equally between two daughter cells. Dysfunctions in cell cycle regulation are associated with birth defects and diseases like cancer.

Laura Lee, M.D., Ph.D., and colleagues identified a new cell cycle regulator: ‘no poles’ (nopo), named for the lack of centrosomes (the “poles” in dividing cells) observed when DNA of nopo-mutant fruitfly embryos stops dividing. The researchers showed that this arrest requires activation of a cell cycle checkpoint – a damage-control system that senses DNA defects and blocks mitotic progression. They also found that NOPO protein, predicted to be an enzyme (a ubiquitin ligase) that modifies proteins to regulate cellular responses, interacts with another ubiquitin system component called BEN.

The findings, reported in the Feb. 1 issue of Development and featured on the cover, support a model in which a NOPO-BEN complex is required during fruitfly embryogenesis for genomic integrity, cell-cycle progression and continuing development.

Leigh MacMillan


Lords of the contractile ring

Cell division requires the formation of a contractile ring. While many protein components of this ring are known, how they interact with each other and with the plasma membrane remains unclear.

Rachel Roberts-Galbraith, Kathy Gould, Ph.D., and colleagues are studying these ring proteins in yeast. One such protein, Cdc15, has two “domains” that carry out different functions – the F-BAR domain, which binds and curves the plasma membrane, and the SH3 domain, which had not been characterized.

In the January Journal of Cell Biology, the researchers show that the SH3 domains of Cdc15 and of another member of the same protein family (Imp2) recruit other proteins (including a paxillin-like protein Pxl1 and a highly conserved C2-domain protein Fic1) to the contractile ring. Together, Pxl1 and Fic1 add structural integrity to the contractile ring and prevent it from fragmenting during cell division. The SH3 domains of Cdc15 and Imp2 overlap in function, and the authors suggest that this redundancy is essential for division of the cellular contents.

Melissa Marino

Past Aliquots

June 22, 2012
June 8, 2012
May 11, 2012
April 27, 2012
April 13, 2012
March 30, 2012
March 16, 2012