Journal Club: Neuroscience, Genetics, and Microbiology

Graduate Division

NEUROSCIENCE: Dissociation of frontotemporal dementia-related deficits and neuroinflammation in progranulin haploinsufficient mice. Filiano, A.J. et al. (Roberson)., Journal of Neuroscience, 33(12):5352-5361.

Degeneration of different parts of the brain result in drastically different results. For example, motor cortex degeneration causes movement problems, hippocampus damage causes memory problems, and frontotemporal degeneration results in changes in behavior and mood.

Mice missing the gene for progranulin are a good model for frontotemporal dementia (FTD), though they also have some level of neuroinflammation as well. Interestingly, humans missing both copies of progranulin don’t have FTD but have a different disease — in humans, FTD occurs with one gene missing but one intact.

Therefore, researchers wanted to compare mouse models between mice without any progranulin and mice with one functional copy of progranulin (haploinsufficient mice). Like the complete knockout mice, the researchers found that the mice with one functional copy still developed social and behavioral problems linked to FTD — however, they did not have neuroinflammation.

GENETICS: A conformational switch in HP1 releases auto-inhibition to drive heterochromatin assembly, Canzio, D. et al. (Narlikar), Nature,  March 13  [epub ahead of print].

Methylation is the adding of a chemical methyl group to regions of DNA in order to control its transcription into mRNA, and therefore is a way to control gene expression. When a region of the genome is modified this way, it becomes “heterochromatin” — meaning that it’s not actively being expressed.

One type of methylation, H3K9, is known to spread from one area of heterochromatin to nearby regions of the genome — but how this happens was unknown. In this paper, researchers found that the protein Swi6 in yeast was essential to the regulation of heterochromatin by H3K9-modified regions.

In some situations, Swi6 was auto-inhibitory and prevented the spread of methylation — but in others, Swi6 promoted the spread of heterochromatin. Overall, the authors conclude that heterochromatin assembly and actin polymerization are similarly regulated, with monomers playing both inhibitory and assembly functions.

MICROBIOLOGY: Endosulfatases SULF1 and SULF2 limit Chlamydia muridarum infection, Kim, J.H. et al. (Engel), Cellular Microbiology., March 11. [epub ahead of print].

For bacteria and viruses to properly infect human cells, they must first bind to the outside of the cell to allow for either uptake by the host cell or invasion by the pathogen. Chlamydia binds to host cells via heparin-sulfate proteoglycans, complex sugary proteins on the host cell’s surface.

Previously, it was thought that the amount of sugar or protein determined how well Chlamydia bound to the cells, but recently it was hypothesized that the amount of sulfation of the proteoglycans was actually an important determinant of bacterial binding.

Here, researchers were able to decrease the amount of sulfation of the sugary proteins by providing host cells with genes for the desulfation of proteoglycans: SULF1 and SULF2. In line with their hypothesis, they found that cells with less sulfation of their surface proteoglycans had less infection with Chlamydia, indicating its necessity for Chlamydia binding and invasion of host cells.