Hope all of you have enjoyed the holidays and managed to get a break from the lab for a few days at least. No break from the JCB though, as we publish our latest issue today. The full table of contents is here, but I've picked out a few selected highlights...
Our festive-looking cover is taken from the paper by Sugimura et al., which shows that the DNA repair protein PARP-1 helps slow down DNA replication forks at sites of DNA damage. As explained in this summary, PARP-1 does this by allowing access to the proteins that repair DNA double-stranded breaks by the process of homologous recombination. The initiation of this pathway delays progression of the replication fork until the DNA is repaired.
Two papers in this issue look at the microtubule plus-end binding protein CLIP-170.Thomas Surrey's group uses an in vitro reconstitution system to study how CLIP-170 and another plus-end binding protein, EB1, dynamically track the growing end of a microtubule. They show that, while EB1 can independently recognize the growing end of a microtubule, CLIP-170 depends on binding to both EB1 and tubulin. Torsten Wittmann discusses the implications of these results in a commentary piece. Meanwhile, Lewkowicz et al. look at the function of CLIP-170 during phagocytosis in macrophages. They find that CLIP-170 is essential for the process and that it regulates actin polymerization by directly recruiting the actin-nucleating protein mDia1.
Away from the cytoskeleton, Gerard Karsenty and colleagues dissect a complicated pathway by which the hormone leptin inhibits the release of insulin from the pancreas. In addition to acting directly on insulin secretion, it seems that leptin also signals via the sympathetic nervous system to stimulate expression of a gene called Esp in bone cells. Esp inhibits the activity of another protein produced by bone cells -osteocalcin - that would usually stimulate pancreatic beta cells to produce insulin. This roundabout route to suppression of insulin is nicely summarized by Mitch here.
Mitch also has a summary of a paper from Sidney Strickland's lab, that shows how degradation of the extracellular matrix can lead to brain damage. It was known that degradation of the ECM protein laminin contributed to neuronal death by overexcitation. But, surprisingly, the group found that mice lacking laminin were actually MORE resistant to brain damage than wild type mice. It turns out that rather than the loss of laminin, it's the proteolytic fragments of the ECM protein that contribute to overexcitation by causing a neuronal receptor called KA1 to be upregulated. Overstimulation of this receptor is likely to be the main cause of cell death.
Finally, I'll just point you in the direction of a great mini-review by Mattias Belting and Anders Wittrup on how nucleic acids are transferred between cells. It's a really quick read and a great introduction to a relatively new field that you may not have read much about. It explains how nucleic acids are transferred between cells through structures such as exosomes, tunneling nanotubes, and apoptotic bodies. These all have implications in both development and diseases such as cancer. Highly recommended!
Plenty more stuff in the issue as well, so take a look. And, of course, have a happy - and successful - New Year!