September 7, 2007

Aliquots — Research highlights from VUMC laboratories

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Parkinson’s cortical connection

The tremors, slowed movements and muscle rigidity of Parkinson's disease result from the death of dopamine-releasing substantia nigra neurons and consequent dopamine depletion in the striatum, a brain region that regulates movement. While the substantia nigra-striatum connection is central to Parkinson's disease, additional connections between the cortex and striatum may modulate the striatal damage associated with dopamine depletion — which includes the loss of dendritic spines on striatal neurons.

Diana Neely, Ph.D., and colleagues examined the role of excitatory cortical inputs on dendritic spines using a co-culture of rat cortex, striatum and midbrain (including the substantia nigra) slices. The investigators confirmed that dopamine depletion decreased striatal spine density. However, removal of the cortex prevented this spine loss, demonstrating a regulatory role for cortical inputs in dopamine depletion-induced spine loss. The results, appearing in the journal Neuroscience, suggest that modulation of cortical activity could represent a novel therapeutic option for Parkinson's disease.

— Melissa Marino

Back to the cell surface

Our cells run a “green” operation: instead of dumping used surface proteins, they recycle them. This process of removing and recycling membrane proteins is critical to proper cell physiology.

James Goldenring, M.D., Ph.D., and colleagues are examining the recycling machinery — the pathways and molecules that move protein cargo to and from the cell surface. In the August issue of Molecular Biology of the Cell, they report that the motor protein Myosin Vb is used in two distinct trafficking pathways in the same cell. Myosin Vb was known to interact with a small G protein called Rab11a to recycle proteins via “clathrin-dependent” pathways. The current studies show that this myosin motor also interacts with another Rab family member, Rab8a, to define a functionally separate recycling system.

The findings support the importance of Rab protein interactions with Myosin V motors in maintaining the cell's surface composition.

— Leigh MacMillan

Clotting factor tied to bone strength

Plasminogen activator inhibitor-1 (PAI-1), the principal inhibitor of the blood clot-busting “plasminogen activating system,” plays roles in a number of ailments including cardiovascular disease and cancer. The factor is also implicated in bone remodeling. While PAI-1 deficiency in humans is rare, PAI-1 excess, which is associated with obesity, insulin resistance and estrogen loss after menopause, is increasingly common, and the effects of excess PAI-1 on bone are unclear.

Sarah Nordstrom, a graduate student working with Douglas Vaughan, M.D., examined the effects of increased PAI-1 expression on bone shape, strength and mineral content in mice. The investigators found that mice that over-express a human variant of PAI-1 showed a 52 percent increase in bone mineral density, and greater biomechanical strength and stiffness compared to control mice. The results, reported in the journal Bone, support a regulatory role of the plasminogen activation system on bone homeostasis, suggesting possible new targets for treating bone diseases.

— Melissa Marino

New home for serotonin

Since serotonin's most celebrated role is its regulation of mood, emotion, sleep and appetite, the central nervous system has been the focus of most research on this signaling system. But serotonin, which was first identified in blood serum, has additional roles in the periphery that are not well understood.

In the early online edition of the American Journal of Physiology-Renal Physiology, Raymond Harris, M.D., and colleagues demonstrate that the kidney also hosts a complete serotonergic system. In rat kidney, the researchers detected expression of both serotonin receptors and transporters as well as the enzymes that synthesize serotonin. They also found that serotonin stimulated expression of growth factors that mediate extracellular matrix accumulation.

Although the normal function of this intrarenal serotonergic system is not clear, the findings suggest a possible role for serotonin as a mediator of renal fibrosis, or scarring, which can lead to kidney failure.

— Melissa Marino

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:

Past Aliquots

June 22, 2012
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April 27, 2012
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March 30, 2012
March 16, 2012