News & Views in 2001

Mature desmosomes are the main adhesive junctions in epithelia and cardiac muscle. Now new work shows that the desmosomal protein desmoplakin is also essential for the maturation of adherens junctions. Desmoplakin clamps down on the transient zippering courtship of the classical cadherins, promoting the maturation of puncta adherens junctions and cortical actin remodelling, steps that are essential for cell adhesion.

Individual viruses have evolved strategies for surmounting a formidable barrier in their path to replication in the nucleus — the nuclear envelope. A new study describing the nuclear entry of adenovirus 2 finds that this virus docks at the CAN/Nup214 protein of the nuclear pore, then hijacks histone H1 and specific H1-import receptors to effect a targeted uncoating of its nucleocapsid at the nuclear pore.

Mitosis in higher organisms requires the dismantling of the nucleus. Reforming the nucleus at the end of mitosis involves the targeting of membranes to chromatin surfaces, followed by fusion to create a closed nuclear envelope. Recent work has identified some of the key players in this fusion process.

Commuters can ride a high-speed mass-transit system from the city centre to the suburbs and then engage a private vehicle for the final leg home. Similarly, vaccinia virions travel to the cell periphery on microtubule tracks, disembark near the plasma membrane, and acquire individual actin tails for propulsion on microvilli towards adjacent cells.

An ever-expanding and diverse collection of proteins and small molecules is involved in the pathways leading to protein disulphide bond formation. However, the origin of oxidative power for this process in the eukaryotic endoplasmic reticulum has remained mysterious. It has now been shown that in the yeast endoplasmic reticulum (ER), the catalyst Erv2p, a member of the Erv1p/ALR protein family, uses molecular oxygen directly to contribute oxidizing equivalents for disulphide bond formation.

Cell proliferation is regulated by temporal changes in gene expression in response to specific chemical and physical cues. These signals are relayed by a variety of intracellular signalling pathways including those activated by small GTPases, such as Ras, Rho, Rac and Cdc42. In this issue, Assoian and colleagues show that Rho confines the expression of cyclin D1 to mid-G1 phase of the cell cycle, by interactions with the ERK and Rac/Cdc42 signalling pathways.

Cytoskeletal attachment to the cell cortex is crucial for mechanical and signalling events at the plasma membrane. The adenomatous polyposis coli (APC) protein, as well as β-catenin in a complex with cytoplasmic dynein, is implicated in mediating such cortical attachment.

Inhibitory neurotransmission by γ-aminobutyric acid (GABA) is regulated by the number and subcellular localization of GABA_A receptors in the membrane of the target neuron. A new study suggests that the ubiquitin-like protein Plic-1 stabilizes intracellular GABA_A receptors and promotes their accumulation in the plasma membrane.

Signalling pathways controlling developmental cell fate rely on a variety of carbohydrate-based protein modifications, including glycosylation of cell-surface and extracellular-matrix proteins. Receptors themselves might be glycosylated during synthesis and secretory trafficking, regulating their subsequent signalling activities. Two recent reports have uncovered a shared requirement for nucleotide–sugar transport in these processes, underscoring the importance of carbohydrates in developmental patterning.

Stem cells have been big news for the past couple of years and yet they remain remarkably inscrutable in terms of declaring their true nature and identity. On p. 778–784 of this issue, Toma et al. describe the identification of a new type of stem cell from the dermis of the skin, called SKP cells. These can be converted into several differentiated cell types in vitro, including neurons, and might become a source of cells for therapeutic tissue repair.

Separase is a protease that cleaves the bonds between sister chromatids during cell division. Until now, separase was thought to be a somewhat repressed protease, cleaving only a few substrates in a very controlled fashion. New findings in this issue raise the possibility that separase has some of the atavistic impulses that characterize caspases, its more destructive relatives.

The notion that a transmembrane receptor at the cell surface can somehow reappear as a transcription factor in the nucleus is bound to be controversial. However, there are two reported examples of this. If this hypothesis can withstand the inevitable and necessary battery of additional empirical tests then our understanding of signal transduction needs to move in a new direction.