New issue roundup: Nov 2nd

There's some really great papers in the latest issue of the JCB - just time for a quick roundup of some of them.

Our cover image this week shows green spots of gamma-TuRC, dotted along the length of red microtubules - a localization you might not expect for a protein complex best known for nucleating the growth of new microtubules from the centrosomes. But Bouissou et al. reveal that gamma-tubulin and its associated proteins also regulate microtubule dynamics. The dots of gamma-TuRC correspond to points at which shrinking microtubules either pause or begin to regrow. Cells lacking gamma-TuRC components show increased microtubule dynamics. As I explain in this summary, the authors think that gamma-TuRC acts as a stabilization factor to limit microtubule disassembly.

Meanwhile, Niault et al. describe a fascinating new way for kinases in different signaling pathways to interact with one another. The Ras-activated kinase Raf-1 inhibits the Rho-activated kinase Rok-alpha. Usually, such inhibitory crosstalk involves one kinase phosphorylating the other, but not in this case. Niault et al. demonstrate that when Raf-1 is turned on, its N-terminal autoinhibitory domain switches from binding its own kinase activity to directly binding and inhibiting Rok-alpha's kinase domain. The authors have previously shown that Ras-induced epidermal tumors rely on Raf-1 to keep Rok-alpha attenuated, in order to promote cell survival and migration - so senior author Manuela Baccarini tells us that she wants to develop small molecules that will block this inhibitory association.

Speaking of tumors being reliant on particular proteins for their survival: Brunelle et al. compare leukemias that depend on two related anti-apoptotic proteins - Bcl-2 and Mcl-1. The group find that the two proteins block tumor cell death by mopping up the same pro-apoptotic factors. Accordingly, mice overexpressing Bcl-2 or Mcl-1 suffer clinically identical leukemias that can only be distinguished using a technique developed by lead author Anthony Letai called BH3 profiling. However, despite their great similarity, Bcl-2 and Mcl-1 dependent leukemias vary greatly in their sensitivity to chemotherapeutic drugs - Mcl-1 protein turns over more rapidly, so provides less protection against cytotoxic agents. Letai now wants to use BH3 profiling to determine the anti-apoptotic dependencies of human tumors and to identify corresponding differences in their response to chemotherapy.

On a completely different note, Loo et al. reveal a surprising heterogeneity in differentiating fat cells. Several markers are upregulated as 3T3-L1 adipocytes differentiate in vitro, but as senior author Steve Altschuler says in this week's In Focus - there's an illusion of correlation. When the researchers looked at individual cells in the population, they realized that the different markers weren't actually increasing in the same cells. Loo et al. ended up identifying four subpopulations of differentiating adipocytes (pictured) which appear to represent distinct stages of adipogenesis. The differentiation process itself occurs asynchronously, so there's always a mix of the 4 cell types giving the false impression that certain markers are upregulated at the same time, when they're actually negatively correlated. It's really worth taking a look at this study, as it shows the limitations of using methods, such as western blotting, that only give an average readout of the population as a whole...

Elsewhere in this issue, Chikashige et al. identify two new proteins required to cluster telomeres into “bouquets” during meiosis. In fission yeast lacking Bqt4, telomeres (magenta) can’t attach to the nuclear envelope (green). Bqt3, on the other hand, protects Bqt4 from protein degradation.

Rif1 was originally identified as a telomeric protein in budding yeast, but has many other roles in the cell. Buonomo et al. delete Rif1 from mice, and discover that the protein facilitates homology-directed DNA repair, particularly at stalled replication forks. Cells lacking Rif1 are thus slower at progressing through S phase. Sticking with the DNA repair theme, Messick and Greenberg  review the many ubiquitination events that occur at double strand breaks - the authors propose that different ubiquitin structures signal different functions that coordinate the repair process.

There's plenty more in the issue too, which you can find on our table of contents, but I'll leave you today with a link to our latest biosights video podcast. This time round, we discuss how melanosomes and endosomes dance together, as Delevoye et al. use electron tomography to reveal the intimate connections between the organelles during melanogenesis. You can watch the brief video, which includes interviews with Cedric Delevoye and Graca Raposo, below or by clicking here.