Journal Club: Recent Research by UCSF Scientists
Alexandra Greer
Science Editor
NEUROSCIENCE: Reduced infarct size and accumulation of microglia in rats treated with WIN 55,212-2 after neonatal stroke. Fernández-López, D., et al. (Vexler). Neuroscience. January 12. [Epub ahead of print]
WIN is a small molecule agonist of cannabinoid receptors; it acts similarly to THC (the active component of marijuana) by activating the CB1R and CB2R cannabinoid receptors found on neurons and immune cells in the brain. WIN has been shown to inhibit neuropathic pain and some neurodegenerative conditions in multiple animal models, making it an attractive potential therapeutic. In addition to pain therapy, researchers wanted to identify whether WIN could be used to ameliorate the effects of cerebral ischemia and stroke. In this paper, researchers induced cerebral ischemia in rats and determined that administration of WIN significantly reduced infarct volume, microglia activation, accumulation, and proliferation at the site of infarct 72 hours after induction of stroke. The authors conclude that WIN ameliorates the effects of stroke mainly through its inhibitory actions on microglia.
CELL BIOLOGY: Membrane Tension Maintains Cell Polarity by Confining Signals to the Leading Edge during Neutrophil Migration. Houk, A.R., et al. (Weiner). Cell. 148(1-2): 175-88.
How do cells know to move in one direction instead of all directions at once? Somehow a cell must be able to promote the formation of a leading edge of the membrane while preventing leading edge formation in all other parts of the membrane. One popular hypotheses of how this works involves the production of molecules that inhibit leading edge formation by the leading edge of a moving cell, but many aspects of this phenomenon remain unknown. However, this paper shows through biological and computational methods that diffusion of inhibitory molecules is not sufficient to prevent other sides of the cell from trying to move forward as well. Instead, they find that plasma membrane tension caused by the formation of a leading edge is sufficient to prevent actin polymerization at other edges of the cell.
GENETICS: An siRNA Screen in Pancreatic Beta Cells Reveals a Role for Gpr27 in Insulin Production. Ku, G.M., Pappalardo, Z., Luo, C.C., German, M.S., McManus, M.T. PLoS Genetics. 8(1):e1002449.
In the search for new drugs targeting type II diabetes, researchers are investigating molecules that regulate insulin production by pancreatic beta cells. Here, researchers created an siRNA library of all mouse G-protein coupled receptors (GPCRs) linked to expression of red fluorescent protein and screened their library with a cell line expressing green fluorescent protein under the control of the human insulin promoter. Therefore, researchers could detect the effects of the inhibition of different GPCRs (through the action of the siRNA) on insulin production by the ratio of red to green fluorescent protein. Interestingly, they found that Gpr27, a GPCR with no known function, positively regulates insulin production.
DEVELOPMENTAL BIOLOGY: Multiple effects of the cellular prion protein on tooth development. Zhang, Y., et al. (Den Besten). International Journal of Developmental Biology. 55(10-12):953-60.
While many people known that prion protein is known for causing infectious neurodegenerative disorders like 'mad cow disease' and Creutzfeldt-Jakobs disease, relatively few people know its normal function when not mutated. In fact, prion protein has been found to be important for proper cell adhesion and for proper signal transduction by Schwann cells in the nervous system. In this paper, researchers identified prion protein in adult human and rodent teeth and wanted to identify the contribution of this protein to the proper development of the teeth. The researchers compared the development of teeth in wild-type and prion protein deficient (Prnp -/-) mice both in vivo and in vitro. In cell culture, dental stem cells proliferated more quickly in Prnp -/- mice compared to controls and in vivo, hardness and mineralization of teeth were altered.
Alexandra Greer is a fourth-year biomedical sciences student.
This article appeared in the February 9, 2012 issue of Synapse.