Journal Club: RImmunology, Cell Biology, Cancer Biology and Neuroscience

Graduate Division

IMMUNOLOGY: Host cell polarity proteins participate in innate immunity to Pseudomonas aeruginosa infection. Tran, C.S., Eran, Y., et al. (Engel). Cell Host Microbe. 2014. 15(5):636-43.

Skin and mucosal surfaces form a critical first barrier to infection. They serve not simply as a passive wall but as a sentry, often detecting impinging pathogens and calling for help from immune cells.               

The opportunistic bacterium Pseudomonas aeruginosa is a frequent and potentially lethal cause of hospital-acquired infections. Previous research has shown that bacterial aggregate binding to the apical surface of epithelium causes it to change to resemble basolateral membrane.

In this paper, Tran and colleagues reported the mechanism underlying this change. They found that the flagellum and type III secretion system needed to be present in the bacteria. They further discovered that binding led to recruitment to the membrane of Par6, Par3, Rac1 and aPKC and that PI3K signaling is required for membrane transformation.

CELL BIOLOGY: The kinase regulator mob1 acts as a patterning protein for Stentor morphogenesis. Slabodnick, M.M. et al. (Marshall).PLoS Biol. 2014. 12(5):e1001861.

Polarization of cells is essential to life—consider the long axons of neurons, the flagella of sperm, or the apical secretion of goblet cells.

Most research on this topic has focused on multicellular organisms, in which both signals from inside and outside the cell control its polarization. Here, however, the authors focused on the extremely large unicellular ciliate Stentor coeruleus, which has a consistent, complex shape.

They first demonstrated that they could effectively use RNA interference to manipulate Stentor. When they used this technique to deplete the kinase Mob1, which is located at the posterior of the cell, they found it led to major defects in cell shape. They also noted that Mob1 was required for the cell to regenerate normally from a small fragment.

CANCER BIOLOGY: Mechanistic rationale for targeting the unfolded protein response in pre-B acute lymphoblastic leukemia. Kharabi Masouleh, B. et al. (Müschen). PNAS. 2014 May 12. Epub ahead of print.

Acute lymphoblastic leukemia (ALL) is one of the most common childhood cancers. It usually develops from cells in the B cell lineage, frequently from the pre-B cell stage.

Recently, a clinical trial found an endoplasmic reticulum (ER) stress-inducing drug had a strong anti-ALL effect. The UPR was not previously known to be important in pre-B cells, but here the researchers found that ablation of this pathway led to the death of normal pre-B cells.

The authors investigated the role of the UPR pathway in pre-B ALL. They found that an inhibitor of XBP1, which is associated with the UPR, killed pre-B ALL cells in vitro and lengthened survival of mice transplanted with pre-B ALL cells. This research further suggests that the UPR pathway may be a useful target for pre-B ALL treatment.

NEUROSCIENCE: Krüppel mediates the selective rebalancing of ion channel expression. Parrish, J.Z., et al. (Davis). Neuron. 2014. 82(3):537-44.

Neurons use multiple ion channels to achieve very particular action potential firing characteristics and receptiveness. Disruption of one ion channel gene generally does not disrupt this state, as the expression of other ion channels adjust to compensate.

The mechanism by which the cells are able to respond to restore normal neural firing properties is not well understood. In this paper, Parrish and colleagues reported their study of this phenomenon in fruit flies.

They showed that loss of the potassium channel Sha1 led to increased expression of the channels Shaker and slowpoke. They found that the transcription factor Krüppel was essential for this response. Moreover, this response was specific in that Krüppel was induced by loss of Sha1 but not in five other potassium channel mutants.