Reviews & Analysis

Some cell-surface receptors activate downstream signal transduction pathways not only from the cell surface but also from endosomes, suggesting that signalling pathways can be regulated by compartmentalization. A further twist is that different internalization routes seem to predetermine whether transforming growth factor β (TGF-β) receptors will trigger a signalling response or be degraded.

Experiments in the yeast Saccharomyces cerevisiae have shown that the enzyme Set1 preferentially targets the 5′ coding regions of transcriptionally active genes, where it catalyses di- and tri-methylation of histone H3 Lys 4. This methylation mark is retained after transcription has subsided, suggesting that it provides a memory of recent transcription.

Chromosome organization in the interphase nucleus is largely regarded to be non-random. However, the exact nature of this non-randomness and the mechanism for conveying positional information to daughter nuclei is a subject of intense debate, as two recent studies reveal.

A distinguishing feature of meiosis is a reductional division where homologous chromosomes — rather than sister chromatids — are pulled to opposite poles. Polo-like kinase (Plk), a prominent regulator of mitotic progression in Saccharomyces cerevisiae, is also crucial in regulating chromosome and chromatid separation during meiosis.

Hearing loss in mammals occurs when auditory hair cells, specialized in the detection of sound waves, undergo irreversible damage. However, the mechanism, and in particular the genetic basis of the process, is poorly understood. A study in this issue now shows that functional inactivation of the cyclin D-dependent kinase inhibitor Ink4d results in progressive hearing loss in mice, implicating Cdk inhibitors and inappropriate hair cell proliferation in deafness.

Chromatin architecture is modulated by a large number of enzymes, resulting in the proper regulation of transcription, replication, cell cycle progression, DNA repair, recombination and chromosome segregation. The structure, regulation and coordination of these enzymatic activities were the main topics of discussion at The Enzymology of Chromatin and Transcription Keystone Symposium held in Santa Fe, NM (March 10–16, 2003).

The ubiquitin-dependent N-end rule pathway targets proteins for degradation through their destabilizing N-terminal residues. This pathway is known to control the import of peptides, chromosome stability and cardiovascular development. A new report identifies yet another function of the N-end rule pathway: the regulation of apoptosis through degradation of Drosophila melanogaster DIAP1.

Sprouty proteins are antagonists of receptor tyrosine kinase (RTK) signalling in a number of developmental and physiological processes. A collection of work indicates that Sprouty proteins negatively and positively modulate RTK-induced signalling pathways through various mechanisms, thereby combining a variety of cellular functions in one molecule.

Cajal described the neural synapse as a “protoplasmic kiss”, and this metaphor applies equally well to the immunological synapse. Viruses are masters at co-opting the machinery of the immune response and, remarkably, the retrovirus HTLV-1 (human T lymphotrophic virus 1) seems to use an immunological-synapse-like structure to conceal viral spread.

The coordinated action of several conserved multiprotein complexes establishes polarity in an asymmetrically dividing cell. How apically localized cues affect the basal distribution of proteins has remained unclear. However, new studies provides a direct link between the two poles, showing that the apical Par6–aPKC complex directly regulates Lethal giant larvae (Lgl).

Cell polarity is regulated by independent pathways that are controlled by Wnt- or Cdc42-mediated signalling. Now, glycogen synthase kinase 3 (GSK-3), an established component of the Wnt pathway, is shown to interact with Par6–protein kinase C ζ (PKCζ), a complex that transduces Cdc42 signals. This exciting result suggests a potential point of conversion between these previously distinct pathways.

Apoptosis is a carefully orchestrated series of events that allows cells to be eliminated without damaging their neighbours. Regulation is essential, as too much apoptosis can contribute to neurodegenerative disorders, whereas too little can result in cancer. Two reports in this issue now demonstrate that Ku70, a protein previously shown to function in DNA repair, has an important role in regulating apoptotic events.

To coordinate the coding complexity of the eukaryotic genome, mechanisms have evolved that protect active genes from silent chromatin structures such as heterochromatin. Although post-translational modifications of histone tails can regulate chromatin states, a new report now demonstrates that the composition of the nucleosome itself is also important for maintaining chromatin states.