Reviews & Analysis

Most cells contain two endogenous clocks, one devoted to the control of cell division and the other acting as circadian pacemaker. Although classically thought to be independent, recent findings challenge this view, as molecular components of the circadian clock directly regulate WEE1, a kinase that inhibits mitosis by inactivating Cdc2/cyclin B.

Polyubiquitination of substrates requires the coordinated and sequential action of three enzymes: E1, E2 and E3. Now, a study shows that activated E2 associates transiently with E3, and that subsequent release of the E2 is functionally required for substrate polyubiquitination.

To ensure genome stability, the S-phase checkpoint blocks spindle elongation during S phase. Later, the spindle assembly checkpoint blocks chromosome segregation by restraining CDC20/Fizzy-dependent activation of the anaphase-promoting complex (APC). Now, a study suggests that the S-phase checkpoint also limits accumulation of Cdc20p and, unexpectedly, an APC-independent CDC20 function for spindle elongation.

An acknowledged key to the success of Mycobacterium tuberculosis as a pathogen is its ability to prevent the fusion of a phagosome containing the internalized bacterium with the host cell's lysosomal system. Recent work examines the modulation of phagosome maturation by addition of exogenous fatty acids and discusses the implications that this could have for anti-tuberculosis therapy or prophylaxis.

The expanding use of small RNA technology to silence specific genes shows no signs of slowing down. However, the discovery that it can induce components of the interferon system in animal cells should make us pause to consider potential non-specific effects of this technique.

A critical attribute of advanced atherosclerosis is the accumulation of free cholesterol in macrophages, triggering cell death. Now, a study reveals that the key events that result in cholesterol-induced macrophage death are the depletion of endoplasmic reticulum calcium stores by free cholesterol and subsequent activation of the unfolded protein response.

In animal cells, cytokinesis is initiated by assembly and ingression of a cleavage furrow, the position of which is determined by signals from the anaphase spindle. Recent work highlights two specialized microtubule populations that may stimulate furrow assembly: inter-zonal microtubule bundles, and astral microtubules that are stabilized by proximity to chromosomes.

Synaptic vesicle recycling is a highly regulated process that involves the coordinated function of several different presynaptic proteins including the dephosphins, whose dephosphorylation is important for triggering endocytosis. Subsequent rounds of endocytosis then depend on rephosphorylation of dephosphins. Recent work establishes Cdk5 as a dephosphin kinase whose function is necessary for synaptic vesicle endocytosis.

Compensatory endocytosis retrieves membrane and proteins that are deposited at the plasma membrane during exocytosis. A new study reveals that actin filaments assemble into structures that compress membrane-bound endocytic compartments formed after exocytosis. This suggests that compressive forces generated by actin polymerization might remodel membranes during secretory and endocytic traffic.

Cells dying by apoptosis acquire 'eat me' signals and lose 'don't eat me' signals to trigger recognition and uptake by phagocytes. How do these sirens of death call the macrophages into a site of massive cell death during tissue remodelling? Release of soluble chemotactic factors, including lysophosphatidylcholine, seems to be the sirens' call.

Cell migration research is taking some intriguing new turns. Emerging studies are revealing marked differences in the way that cells migrate in two versus three dimensions, plasticity in their migration mechanisms and diversity in the contribution of different Rho family GTPases that drive various modes of migration.

The physical link between integrin adhesion receptors and the actin cytoskeleton mediates bidirectional transmission of force and biochemical signals across the plasma membrane. This link is essential for the development and function of multicellular animals. Recent work reveals that the integrin-associated actin-binding protein talin provides the initial connections between integrins and the cytoskeleton, establishing a pivotal role for this connection in bi-directional integrin signalling.