Time for another new issue roundup, and let's start - as usual - with our cover story or, to be precise, our cover stories. Two papers from Björn Öbrink's lab in Stockholm dissect the mechanism by which a homophilic cell adhesion molecule transmits information across the plasma membrane. It wasn't actually known how molecules like CEACAM1 - a member of the Ig domain superfamily - send signals into the cytoplasm when they adhere to neighboring cells. Klaile et al. and Müller et al. show that when CEACAM1 molecules self-interact across opposing membranes, they undergo a conformational change that prompts them to form homodimers within the same membrane. CEACAM1 homodimers recruit a tyrosine phosphatase to their cytoplasmic tails at the expense of c-Src, triggering signaling events inside the cell. You can read a slightly more in-depth summary of the two papers, and learn why Öbrink thinks other cell adhesion molecules may act similarly, in this month's In Focus feature.
Meanwhile, Hayashi et al. demonstrate that heparan sulphate glycoproteins maintain stem cell niches in Drosopila. Dally is required to keep female germ stem cells in their specialized microenvironment, while dally-like plays the same role for male germ stem cells. The image above shows how the germ cells are missing from an ovariole lacking dally. On the other hand, a fascinating paper from Wu et al. suggests that mammalian male germ stem cells may not need a specialized niche at all to retain their stemness - it might just come down to chance instead. Sperm stem cells and their differentiating progeny lie next to each other on the basement membranes of seminiferous tubules, with no discernible differences in their microenvironments. Wu et al. show that this situation can be replicated in vitro - a homogeneous culture can sustain both stem cells and their progeny and the proportion of each cell type remains constant over time. The researchers suggest that the decision to differentiate or self-renew is simply a stochastic choice and show mathematically that a 33% chance of differentiating would account for the numbers of each cell type seen in culture. However, as Zhuoru Wu explains in this summary, this doesn't mean that the environment has no impact on cell fate decisions - external stimuli might alter that 33% probability of differentiating.
Switching gears, Lleres et al. present a new method of measuring the levels of chromatin condensation in living cells. The assay measures FRET in cells expressing both GFP and mCherry tagged histone proteins. In the image to the right, different levels of FRET efficiency are pseudo-colored to distinguish regions of the nucleus with distinct degrees of compaction - the arrows indicate highly condensed chromatin (red) at the nuclear periphery.
Elsewhere in this issue, we learn from Munck et al. about a protein that coordinates peroxisome biogenesis and inheritance. Like Chang et al. a few weeks ago, Munck and colleagues show that Pex3 - a protein known for its role in peroxisome formation - also helps divide copies of the organelle between mother and daughter yeast cells. Munck et al. show that Pex3p recruits a protein called Inp1p to peroxisomal membranes, which helps to retain the organelle in the mother cell by anchoring them to the cell membrane.
New peroxisomes form from the endoplasmic reticulum. This latter organelle is the focus of Schuck et al.'s attention: they're interested in why the ER expands in response to stress. Here, they show that the increase in size is controlled by regulators of lipid synthesis and by the unfolded protein response - the standard stress response that also upregulates chaperone proteins. However, ER expansion alone can alleviate stress even in the absence of chaperone production. Sebastian Schuck suggests in this summary that the larger ER may serve to dilute the concentration of unfolded proteins, preventing them from aggregating in the ER lumen.
Sticking with the secretory pathway, we take a journey through the Golgi - a meeting report from a host of top-notch Golgi researchers who all met earlier this year to discuss the current state of the field. It's a subject that's close to my heart as I worked on the Golgi for my PhD, and this review nicely summarizes the researcher's current thoughts on 4 key questions: how are proteins transported through the Golgi?; what are the connections between Golgi cisternae?; what role do distinct membrane domains play?; and, above all, is the Golgi an independent organelle? On top of that, the review outlines key questions for the future, so be sure to read it if you're at all interested in the Golgi and secretion.
Finally for today, Cianciola and Carlin reveal how an adenoviral protein called RID-alpha induces a cholesterol trafficking pathway in its host cells. Intriguingly, the protein actually helps to correct the lipid-sorting defects seen in the lysosomal storage disease Niemann-Pick type C. But I shan't go into any more detail here, as you can listen to senior author Cathleen Carlin explain all to Eun Choi in the latest episode of our biobytes podcast. which is also out today. In the same episode, you can hear David Salomon tell me about the crosstalk his lab has discovered between the Notch and Nodal signaling pathways (Watanabe et al.) and Deepta Bhattacharya describe how hematopoietic stem cells frequently exit their niche in the bone marrow without undergoing cell division (Bhattacharya et al.). You can listen below, or subscribe to the monthly podcast in iTunes by clicking here. And don't forget to check our full table of contents for everything I didn't have time to discuss here...
that, in turn, activates the IP3R calcium channel and subsequent calcium release. As senior author Ira Tabas 