Journal Club: Immunology, Cell Biology, and Neuroscience

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Graduate Division

IMMUNOLOGY: T-cell activation induces proteasomal degradation of Argonaute and rapid remodeling of the microRNA repertoire. Bronevetsky, Y. et al. (Ansel). Journal of  Experimental Medicine. 210(2):417-32.

MicroRNAs are short RNA molecules that regulate the expression of certain genes by binding to messenger RNA before it is translated, causing its degradation. MicroRNAs bind to their targets because they are complementary to their messenger RNA target, so each regulated gene must have its own microRNA.

It’s a fast way to regulate a gene’s expression, because the microRNA doesn’t need to be transcribed into protein (which takes longer). During T-cell development, the expression of many genes changes and is correlated with a global down-regulation of microRNA levels.

In this paper, researchers showed that the down-regulation of microRNA occurs through ubiquitination and proteasomal degradation of Argonaute, a protein found in the microRNA-induced silencing complex. Furthermore, they found that down-regulation of microRNAs through Argonaute caused naïve T-cells to more easily undergo differentiation into cytokine-producing helper T-cells.

CELL BIOLOGY: β(1)-adrenergic receptor antagonists signal via PDE4 translocation. Richter, W.; Mika, D.; Blanchard, E.; Day, P.; Conti, M. EMBO Reports. February 5. [Epub ahead of print]

Cyclic AMP, or cAMP, is a signaling molecule in cells that must remain in a tight balance for cells to function properly. Increased cAMP is typically the result of receptor or protein activation and can mediate downstream gene expression.

cAMP levels are regulated through processes of both cAMP production, by adenylate cyclases, and cAMP degradation, by phosphodiesterases. Typically, receptor activation causes adenylate cyclases to increase cAMP production, thereby mediating downstream effects.

In this paper, researchers describe how the B(1)-adrenergic receptor mediates its downstream effect through inactivation of a phosphodiesterase, PDE4. Inactivation of the phosphodiesterase causes accumulation of cAMP, which allows for mediation of downstream effects, much as an increase in cAMP production would do.

NEUROSCIENCE: Erythropoietin increases neurogenesis and oligodendrogliosis of subventricular zone precursor cells after neonatal stroke. Gonzalez, F.F. et al. (Ferriero). Stroke. February 7. [Epub ahead of print]

Neonatal stroke, which occurs in roughly 1 in 4,000 births, is a leading cause of neonatal brain injury and can result in cerebral palsy and developmental delays. Treatment for neonatal stroke is controversial because of the potential for severe complications, and many strokes go unnoticed because of incomplete symptoms.

Erythropoietin (EPO) is a hormone involved in neuronal development that has shown promise in treatment of brain injury in animal models, and is being investigated for treatment of neonatal stroke because of its potential for avoiding the dangerous side effects associated with blood-thinning stroke treatments.

In this paper, researchers investigated the use of EPO in treatment of stroke in rats, and looked for regeneration of neural progenitor cells in the subventricular zone of the brain. With EPO treatment, the rats had increased cellular regeneration, which makes EPO an attractive candidate for new neonatal stroke therapy.

CELL BIOLOGY: FOXO3A directs a protective autophagy program in haematopoietic stem cells. Warr, M.R. et al. (Passegué). Nature. February 6. [Epub ahead of print]

Our red blood cells and many critical component cells of our immune system have a  short lifespan in our blood and need to be constantly renewed. This renewal, which requires a huge expenditure of energy, takes place thanks to the actions of haematopoietic (“blood-making”) stem cells (HSCs) present in the bone marrow.

These rare cells are constantly churning out daughter cells that develop into different types of blood cells, including red blood cells and many immune cells. Because of their crucial role in the health of the organism, it is important that HSCs maintain their survival in times of stress, such as disease or starvation.

In this paper, researchers found that in times of stress, HSCs rapidly begin a program of autophagy (that is, consuming themselves) to maintain the health of the cell, and that the gene FOXO3A orchestrates this rapid response to stress.