Journal Club: Microbial Pathogenesis, Cancer Biology, Neuroscience, and Immunology

MICROBIAL PATHOGENESIS: The microRNAs in an ancient protist repress the variant-specific surface protein expression by targeting the entire coding sequence. Saraiya, A.A., et al. (Wang). PLoS Pathog. 2014. 10(2):e1003791.       

Ingestion of the flagellated protozoan Giardia lamblia causes giardiasis, a disease with a rhyming sobriquet, "beaver fever," and the rather unpleasant major symptom of slow-to-resolve diarrhea.

Giardia switches between numerous variants of its surface proteins (VSPs), effectively disguising itself from the immune system. Previous studies have found that all VSPs are being transcribed at once, with regulation hypothesized to occur largely through microRNAs (miRNAs) degrading all but a few of the variants.

In this paper, Saraiya and colleagues identified 99 new probable miRNAs as well as sites in all 73 VSPs that are likely targeted by these miRNAs. They further showed that full repression of a given variant requires the combined action of several miRNAs specific for it. Notably, some of miRNA-targeted sites are within coding sequence of the targeted RNA. 

CANCER BIOLOGY: The chromatin regulator Brg1 suppresses formation of intraductal papillary mucinous neoplasm and pancreatic ductal adenocarcinoma. von Figura, G., et al. (Hebrok). Nat Cell Biol. 2014. 16(3):255-67.

Each year, a few hundred thousand people die from pancreatic cancer, which is notoriously difficult to treat. The most common form of pancreatic cancer, pancreatic ductal adenocarcinoma (PDA), originates from any of three distinct types of precursors, including intraductal papillary mucinous neoplasms (IPMNs). 

The genetic differences between these three subtypes of PDA have remained poorly understood, though previous research has found that Brg1, which is part of a chromatin-remodelling protein complex, is frequently mutated in IPMN-derived PDA.

In this article, the authors reported that pancreatic deletion of Brg1 in mice, in the presence of mutant Kras, leads to the formation of cystic neoplasms reminiscent of IPMN. They further found that these lesions developed into PDA and that, as with IPMN-PDA in humans, this PDA had a better prognosis than another type of PDA.

NEUROSCIENCE: Axonal Control of the Adult Neural Stem Cell Niche. Tong, C.K., et al. Cell Stem Cell. 2014 Feb. 19. Epub ahead of print.

What was once dogma—that no new neurons were produced after birth—has been fully upended over the last two decades. It is now clear that neural stem cells can be found in a region of the adult brain called the ventricular-subventricular zone.

Although much work has been done in characterizing these neural stem cells (NSCs), the role of fully developed neurons on these NSCs has not been characterized well.

Here, Tong and colleagues reported a role for nerve impulses in regulating these NSCs. They found that a population of distant serotonin-producing neurons synapse with the NSCs, that the NSCs express receptors for serotonin, and used pharmacologic targeting of these receptors to show that receptor signaling correlates with proliferation. 

IMMUNOLOGY: Serum IgE clearance is facilitated by human FcεRI internalization. Greer, A.M., et al. (Shin). J Clin Invest. 2014. 124(3):1187-98.

The watery eyes, itchy rash, or tight throat of an allergic reaction are due to binding of the allergen to IgE, a type of antibody, bound to the receptor FcεRI on the surface of basophils and mast cells.

An alternative form of this receptor is also expressed on other white blood cells in humans, including dendritic cells and monocytes, but the role of the receptor on these cells has been wholly unknown.

In this article, Greer (longtime former writer of this column) and colleagues reported that IgE that binds to dendritic cells is taken up rapidly and degraded; this is unlike basophils, in which the IgE remains on the surface for an extended period of time. They further found that mice with human FcεRI rapidly clear circulating IgE and that this clearance depends on dendritic cells and monocytes.