Planar polarity: location,location, location

Recent studies have shown that many proteins that regulate planar polarity in the fly eye are organized into discrete membrane sites which may be crucial for coordinating groups of cells.     

DNA-damage checkpoints: location, location, location

The DNA-damage response (DDR) is an evolutionarily conserved signaling cascade crucial for sensing DNA damage and activating cellular responses such as cell-cycle arrest, DNA repair, senescence and apoptosis. Excitingly, two recent studies describe activation of this checkpoint in the absence of DNA damage. These studies support the idea that accumulation of checkpoint proteins and changes in global-chromatin structure are important signaling intermediates for the activation of the DDR.     

Location, location, location..

Intra-abdominal fat is an established risk factor for the metabolic syndrome. In this issue of Cell Metabolism, Tran et al. (2008) test the cell-autonomous and location-related properties of transplanted intra-abdominal and subcutaneous fat depots. While subcutaneous fat seems to confer metabolic benefits, species differences in adipose biology justify caution in interpreting the results.     

Growth factor receptor signalling: location, location, location

Ligand binding to plasma membrane receptors initiates a series of events culminating in a variety of changes in cellular phenotypes. Although numerous publications have documented the activation/inactivation of signalling molecules following receptor binding, relatively few investigations have focused on the cellular compartment responsible for either initiating or selecting the particular pathway that mediates the response. Specifically, does receptor signalling occur only at the plasma membrane; is signalling dependent upon the location of defined endosome populations; or are components of both plasma membrane and endosomal activity operative depending upon the particular signalling pathway or cell type? This review addresses aspects of these questions by discussing the evidence supporting or contrasting the interplay between the endocytic and signalling systems for a subset of tyrosine kinase, serine/threonine kinase and G-protein-coupled receptors.     

Regulating TERT: Location,location, location

Comment on: Mechanism of dominant-negative telomerase function.

Binh N. Nguyen, Lynne W. Elmore and Shawn E. Holt. Cell Cycle 2009; 8; In press.     

The three most important things about origins: location,location, location

The reasons why some DNA replication origins fire earlier than others have remained elusive. New work by Gindin et al suggests that the distribution of replication origins, not their timing per se, is the major determinant of the timing of genome replication in human cells.     

Location,location, location? No. Catalog number

Once you start to read this Editor’s Corner, you might wonder why I have devoted an entire article, albeit a short one, to this topic. Let me assure you there are reasons. First, I want to announce a new policy for the journal that will affect all research papers. Starting with all papers that are not currently in press, we will no longer be asking for geographical locations of research companies that follow the listing of a reagent. In Materials and Methods the authors typically refer to a reagent and then list the company and its location parenthetically. For example, “…p-nitrophenyl phosphate (Sigma-Aldrich, St. Louis, MO).” Instead, we will require catalog numbers. The reason is that it is now quite easy to find a company using the internet, and in fact you rarely need to know the location because it is rare that you would send a written order. On the other hand, knowing the name of the reagent is not always sufficient to narrow down the precise item. For example, if you search for “p-nitrophenyl phosphate” at the Sigma-Aldrich site, you get seven primary choices and it is not at all obvious which one to choose. When my lab uses p-nitrophenyl phosphate for the Pho8?60 assay, we use item N9389, which narrows it down to a precise reagent. Thus, we will start requiring papers to write “…p-nitrophenyl phosphate (Sigma-Aldrich, N9389).

Second, I think this is actually a useful change, and one that many journals will start to institute once they see it being done here. The old style of listing the city and state is a relic that is no longer relevant. Furthermore, it is not even clear in the current global marketplace if this is particularly helpful. For example, if I am ordering an item from Roche Applied Science, why would anyone care where it is coming from? It is highly unlikely that a researcher in Germany or Japan is going to order from Roche Applied Science that happens to be based in Indianapolis, IN when there are much closer sites in Mannheim, Germany and Tokyo, Japan. So, do not be surprised when you start to see more and more journals adopting this approach, and remember that you saw it here first. Autophagy—the cutting edge.     

Location, location, location: the cancer stem cell niche

The existence of a stem cell niche, or physiological microenvironment, consisting of specialized cells that directly and indirectly participate in stem cell regulation has been verified for mammalian adult stem cells in the intestinal, neural, epidermal, and hematopoietic systems. In light of these findings, it has been proposed that a "cancer stem cell niche" also exists and that interactions with this tumor niche may specify a self-renewing population of tumor cells. We discuss emerging data that support the idea of a veritable cancer stem cell niche and propose several models for the relationship between cancer cells and their niches.     

Location, location, location: new insights into O-GalNAc protein glycosylation

O-GalNAc glycosylation of proteins confers essential structural, protective and signaling roles in eumetazoans. Addition of O-glycans onto proteins is an extremely complex process that regulates both sites of attachment and the types of oligosaccharides added. Twenty distinct polypeptide GalNAc-transferases (GalNAc-Ts) initiate O-glycosylation and fine-tuning their expression provides a mechanism for regulating this action. Recently, a new mode of regulation has emerged where activation of Src kinase selectively redistributes Golgi-localized GalNAc-Ts to the ER. This relocalization results in a strong increase in the density of O-glycan decoration. In this review, we discuss how different mechanisms can regulate the number and the types of O-glycans decorating proteins. In addition, we speculate how Src-dependent relocation of GalNAc-Ts could play an important role in cancerous cellular transformation.     

Location,location, location: translational control in development and neurobiology

Control of gene expression by regulating mRNA translation is essential for proper growth and development in species ranging from yeast to mammals. Recently, translational regulation has also been implicated in neuronal function, where long-lasting changes in synaptic strength and the formation of memory require new protein synthesis. Crucial to both developmental and neurobiological function, translational control allows for the asymmetric distribution of gene products and a rapid and local response to stimulation--as discussed at a recent Serono Foundation EMBO Workshop held in Mallorca, Spain.