Journal Club: Microbiology, Structural Biology, Cell Biology and Developmental Biology

Wednesday, November 19, 2014

MICROBIOLOGY: The Pseudomonas aeruginosa type III translocon is required for biofilm formation at the epithelial barrier. Tran, C.S., et al. (Engel). PLoS Pathog. 2014. 10(11):e1004479.

Bacterial infections become harder to treat when the bacteria form biofilms—dense aggregates of bacteria and extracellular matrix. The bacterium Pseudomonas aeruginosa is a potentially fatal opportunistic pathogen that often forms biofilms in the course of its infection.

Previous studies of Pseudomonas biofilms have focused on examining how it forms on plastic and other artificial surfaces. In this paper, the authors studied biofilms made in vitro on layers of epithelial cells.

They found that a molecular apparatus for secreting toxins was required to form biofilms on epithelial cells but not artificial surfaces. The toxins typically secreted through this apparatus, however, were not required. Intriguingly, the researchers demonstrated that an as-yet-unidentified factor released from the epithelial cells after pore formation was induced by the bacteria contributed to biofilm formation.

STRUCTURAL BIOLOGY: Subnanometre-resolution electron cryomicroscopy structure of a heterodimeric ABC exporter. Kim, J., et al. (Cheng). Nature. 2014 Nov. 2. Epub ahead of print.

ABC transporters are a family of proteins that move a range of molecules across cell membranes in organisms from bacteria to humans. Certain ABC transporters can export drugs from the cell, which can contribute to cancers and bacteria resisting treatment.

The structures of several ABC exporters have already been determined using x-ray crystallography, but the manner in which these proteins move in the course of exporting a molecule remains debated. Now, Kim and colleagues have used a complementary method for examining tiny structures, cryo-electron microscopy, to examine an ABC exporter.

Their results show that the base state is open toward the interior of the cell. They further suggested how particular sliding motions of parts of the protein would allow it to then transition to outwardly open as it exported its target molecule.

CELL BIOLOGY: Spatial encoding of cyclic AMP signaling specificity by GPCR endocytosis. Tsvetanova, N.G. & von Zastrom, M. Nat Chem Biol. 2014 Nov. 2. Epub ahead of print.

Epinephrine acts on cells by binding to its receptor, leading to production of the intracellular signaling molecule cAMP. Ligand binding to many other members of the same protein family as this receptor also causes cAMP production.

After binding, the receptors are taken up into the cell, where recent work has shown that additional cAMP can be produced—now near endosomes instead of near the plasma membrane. In this paper, the authors found that location matters: cAMP produced in different locations has different effects.

They found that preventing receptor endocytosis prevented certain downstream events, even when the amount of cAMP in the cell was the same. Conversely, they selectively induced cAMP production at endosomes and found it had different effects than cAMP production at the plasma membrane.

DEVELOPMENTAL BIOLOGY: Ezh2-mediated repression of a transcriptional pathway upstream of MMP9 maintains integrity of the developing vasculature. Delgado-Olguin, P. et al. (Bruneau). Development. 2014 Oct. 30. Epub ahead of print.

Sometimes it's normal to have a leaky blood vessel—at the site of an infection, for example—but too much leakiness, not surprisingly, can cause problems. Blood vessel cells rely on the extracellular matrix, a network of collagen and other fibers, to stabilize them.

This paper from the Bruneau group opens with the observation that disabling Ezh2, which tends to repress genes, in blood vessels leads to death before birth. A genome-wide assay reveals that Ezh2 represses activators of MMP9, a protein that digests extracellular matrix, leading to decreased vascular integrity.

The authors hypothesize that perhaps this pathway that control MMP9 is implicated in certain diseases with defects in vascular integrity.