Reviews & Analysis

Semaphorins regulate a variety of biological processes, including axon guidance, neuronal migration, angiogenesis, cardiogenesis and immune responses. Semaphorin 6D is now shown to regulate osteoclast function during bone development, through its association with its receptor plexinA1. This activity implicates a signalling pathway known to transcriptionally regulate cell differentiation and involves the receptor Trem2 and the adaptor DAP12.

The recent discovery of many new mammalian DNA polymerases has left researchers trying to assign their biological functions. Surprising evidence has just emerged indicating that DNA polymerase κ, an enzyme implicated in the bypass of replication blocks, has a role in gap-filling synthesis during nucleotide excision repair (NER) of DNA adducts.

Dosage compensation in Drosophila melanogaster is distinguished by the hypertranscription of the male X chromosome. New findings show that this process requires the nuclear pore complex.

Endocytosis in eukaryotic cells involves numerous specialized protein complexes and lipid domains. One particularly intriguing protein is dynamin, a large GTPase that is very different from other GTPases. Now, phospholipase D has been identified as surprising regulator of dynamin's GTPase activity.

Accurate segregation of genetic information during cell division relies on a multiprotein complex called the kinetochore, whose formation requires specialized centromeric chromatin. Two papers in this issue of Nature Cell Biology identify a multitude of new vertebrate kinetochore proteins that provide insight into the link between centromeric chromatin and the kinetochore, and suggest a functional relationship between centromeres and nucleoli during interphase.

During cell division, replicated DNA condenses into chromosomes that conspicuously align at the equator of the microtubule-based spindle. This alignment is important for accurate chromosome segregation to daughter cells and startling new data show that chromosomes cooperate with one another to achieve this alignment.

Monoubiquitination of the processivity clamp, PCNA, facilitates the replicative bypass of DNA lesions by recruiting damage-tolerant polymerases. In undamaged cells, deubiquitination of PCNA by the deubiquitinating enzyme USP1 reveals a possible safeguard mechanism against the mutagenic effect of these polymerases. Intriguingly, USP1 itself seems to be downregulated by a damage-induced autocatalytic cleavage event.

Bone Morphogenetic Protein (Bmp) signalling has a critical function in patterning vertebrate and invertebrate embryos. A key regulator of Bmp signalling is Chordin, which binds Bmps and prevents them from interacting with their receptors. Two new papers identify the Frizzled-related protein Sizzled as an unexpected regulator of Chordin stability.

Gas exchange between the plant and the atmosphere depends on the opening of pores located primarily on the surfaces of leaves. A protein that regulates pore opening in response to both atmospheric CO₂ concentrations and blue light has now been identified.

In mammals, the germ-cell lineage separates from the somatic lineages around the time of gastrulation. Primordial germ cells migrate to the developing gonads and become the source of future gametes. Surprisingly, skin stem cells also have the intrinsic ability to develop into oocytes.

Actin is the most abundant protein in the giant oocyte nucleus of the frog Xenopus. It reaches this high concentration because the oocyte lacks exportin-6, a nuclear export factor that specifically pumps actin out of other nuclei. What effect actin has on the physical properties of the oocyte nucleus is a matter of ongoing debate.

At the onset of mammalian X-chromosome inactivation, the X chromosomes are counted and then a choice is made about which one to inactivate. New findings provide evidence that a transient physical association between X chromosomes in the nucleus might be involved in this process.

The anaphase-promoting complex/cyclosome (APC/C) is a ubiquitin ligase that controls cell-cycle progression by targeting proteins for destruction by the 26S proteasome. The APC/C is active throughout late mitosis and G1 phase but APC/C substrates are degraded in a specific order. A recent study provides insights into how ordered turnover of substrates is achieved.

Embryonic stem (ES) cells deficient in Mbd3, a component of the nucleosome remodelling complex (NuRD), exhibit LIF-independent self-renewal and a restricted potential to differentiate. As such, it is likely that NuRD is required for ES cell pluripotency, and represents a potential link between maintaining the undifferentiated state and the capacity to differentiate.

Leukocyte recruitment from blood to areas of infection is a key step in both innate and adaptive immunological responses. The predominant model has been that leukocytes transmigrate through the junctions between adjacent endothelial cells. However, leukocytes can also migrate through the endothelial cells, and new insights suggest that both caveolae and intermediate filaments are important for this.