January 25, 2008

Aliquots — Research highlights from VUMC laboratories

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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.

Mutant worms get that sinking feeling

Cellular “vacuum cleaners” known as dopamine transporters (DATs) are found on neuronal membranes where they regulate extracellular dopamine levels, sopping up excess neurotransmitter and limiting “spillover” to neighboring synapses. The roundworm C. elegans, an indispensable animal model for studying synaptic signaling, has its own DAT, called DAT-1, but its specific function in vivo remains unclear.

In the Journal of Neuroscience, Randy Blakely, Ph.D., and colleagues report that DAT-1 disruption causes worms to become prone to paralysis when challenged to exert maximal physical activity; worms lacking DAT-1 become progressively paralyzed and sink rather than swim, whereas normal worms continue swimming vigorously. This swimming-induced paralysis derives from spillover of dopamine to extrasynaptic dopamine receptors that in turn act to block movement. Additionally, they show that proper clearance of dopamine depends on efficient trafficking of DAT-1 to the synapse. Further investigations of this paralysis may help researchers further probe the role of dopamine and DATs in the whole animal.

— Melissa Marino

Beans, beans good for diabetes?

The prevalence of type 2 diabetes is rapidly increasing worldwide, necessitating the importance for development of prevention strategies. Studies have theorized a beneficial role for legumes in preventing type 2 diabetes, but data directly linking the two have been limited.

Raquel Villegas, Ph.D., Xiao Ou Shu, M.D., Ph.D., and the Shanghai Women's Health Study research team investigated the effect of dietary legumes and soy food intake on the incidence of type 2 diabetes in a large population-based prospective cohort study of 75,000 middle-aged Chinese women in urban Shanghai. This study, recently published in the American Journal of Clinical Nutrition, found that total legume consumption, including soybeans, peanuts and soymilk consumption, was associated with a decrease in type 2 diabetes. Women whose legume consumption was in the top 20 percent had a 38 percent lower risk of developing diabetes than those whose intake was in the lowest 20 percent. This study adds to evidence that legume consumption potentially has a beneficial effect in preventing type 2 diabetes.

— Susanne Tranguch

Enzyme links cilia and asymmetry

From the outside, the two halves of the vertebrate body may look like mirror images. But on the inside, organs show a distinct asymmetry — with some organs on the left and others on the right. Previously, Susan Wente, Ph.D., and colleagues showed that Ipk1, an enzyme involved in the synthesis of an important cell-signaling molecule called IP6, helps govern this “left-right asymmetry.”

In a recent issue of the Proceedings of the National Academy of Sciences, Wente and colleagues suggest a possible mechanism by which altered Ipk1 levels affect left-right asymmetry in zebrafish embryos. They show that knocking down Ipk1, and therefore IP6 levels, reduces the length and inhibits the beating of cilia — microscopic finger-like cellular projections that function in movement and sensation — in organs involved in establishing zebrafish asymmetry. Their findings demonstrate a new role for Ipk1 in mediating cilia function, ultimately having implications for diseases associated with defective ciliary function, like polycystic kidney disease.

— Susanne Tranguch

Local ‘catastrophes’ move cells

Microtubules — part of the cell's structural skeleton and cargo-moving system — are nearly always in flux. They grow, shrink, and rearrange themselves as they participate in processes including cell division and cell migration.

Irina Kaverina, Ph.D., and colleagues are exploring the mechanisms regulating microtubule dynamics. They previously observed an interaction in migrating cells between microtubules and structures called focal adhesions. In the Jan. 15 Journal of Cell Science, they report that “microtubule catastrophes” — transitions from growth to shrinkage of microtubules — are enriched at focal adhesion sites. In addition, the investigators find a role for the scaffolding protein paxillin in the microtubule catastrophes: they suggest that paxillin tethers a putative “catastrophe factor” and/or regulates its access to microtubules.

Understanding how localized microtubule catastrophes are involved in cell division and migration could shed light on the mechanisms of microtubule-targeted cancer therapies like colchicine, vincristine and paclitaxel (Taxol).

— Leigh MacMillan

Past Aliquots

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