UCSF Journal Club: Recent Research by UCSF Scientists
Alexandra Greer
Science Editor
MICROBIOLOGY: Chlamydia trachomatis co-opts the FGF2 signaling pathway to enhance infection. Kim, J.H.; Jiang, S.; Elwell, C.A.; Engel, J.N. PLoS Pathogens 7(10):e1002285.
Heparan sulfate proteoglycans (HSPGs) are sugar molecules found on the surfaces of essentially all animal cells. They mediate a multitude of different processes, such as blood coagulation, cell-cell recognition, and are even used by some pathogens – including chlamydia– to gain entry into our cells. While it has been known that chlamydia requires HSP interaction to gain entry into cells, it was not clear how this occurs. In this paper, researchers found that cell entry requires the binding of host fibroblast growth factor 2 (FGF2) to its FGF receptor on the host cell – a process that also typically requires HSPG interaction. FGF2 present outside of the host cell binds to the bacterial cell, which allows for the bacteria to get stuck to a host mammalian cell via binding of FGF2 to its receptor. This binding induces internalization of the receptor:ligand complex along with the bacterium.
IMMUNOLOGY: Basal LAT-diacylglycerol-RasGRP1 signals in T cells maintain TCRα gene expression. Markegard, E. et al. (Weiss, Roose) PLoS One 6(9):e25540.
Throughout a naïve T-cell’s lifetime, it receives signals via its T-cell receptor (TCR). Some of these signals are strong and induce activation of the cell, but others are weaker and are intended to remind the cell to stay alive. Without constant, low-level signaling via the TCR, a naive T-cell will die of neglect. While we understand the signaling pathways behind strong, activating TCR signals, we understand much less about the signaling pathways involved in low-level, survival signaling. Here, researchers have identified the signaling adaptor LAT and RasGRP1 in transducing low-level, non-activating signals that maintain TCR expression in the cell. The researchers propose that this low-level signaling serves to regulate TCR expression in the T-cell, thereby controlling the potential for further T-cell activation.
NEUROSCIENCE: Corridors of migrating neurons in the human brain and their decline during infancy. Sanai, N. et al. (Rowitch, Alvarez-Buylla) Nature [epub ahead of print].
Since it was shown roughly a decade ago that adult neurons in the mouse brain can regenerate, there has been both significant research and significant controversy surrounding which types of neurons can initiate this, where they move from and to, and at what developmental stages they promote regeneration. In non-human mammals, it has been shown that immature neurons found in the subventricular zone (SVZ) of the brain migrate in large groups to the olfactory bulb. However, in humans there remains controversy over whether adult human SVZ astrocytes can generate neural cells or migrate in vivo. Here, researchers have found an extensive corridor of migrating immature neurons in the SVZ of human infants destined for both the olfactory bulb and the prefrontal cortex that diminishes almost entirely into adulthood, thereby settling much controversy and introducing the possibility for treatment of neonatal neurological injury.
MICROBIOLOGY: Proteomic analysis of human skin treated with larval Schistosome peptidates reveals distinct invasion strategies among species of blood flukes. Ingram, J. et al. (McKerrow). PLoS Neglected Tropical Diseases 5(9):e1337.
Shistosomes are a genus of parasitic worm that burrow into the skin and cause chronic disease and are very common in tropical areas of Africa. To get into its host, the worm burrows into otherwise healthy skin by essentially ‘digesting’ its way through – by releasing proteolytic enzymes that allow the worm to penetrate the skin and burrow inside. S. mansoni, which is the most common shistosome parasite, uses the enzyme cercarial elastase to digest elastin in our skin– but it is not known what enzymes other shistosomes use. Here, researchers performed proteomic analysis of human skin biopsies treated with either cercarial elastase or an enzyme hypothesized to digest elastin from the closely relates Shistosoma japonicum to determine substrates of each enzyme. They found that similar proteins in human skin were digested by the two enzymes and suggest that the gene for cercerial elastase underwent genetic amplification in the process of adapting to humans.
Alexandra Greer is a fourth-year biomedical sciences sudent. For comments or paper suggestions, email alexandra.greer@ucsf.edu.
This article appeared in the October 20, 2011 issue of Synapse.