Cells' puncture repair kit

Origins of mitotic inequality A ll cells are not equal, at least when it comes to the length of the cell cycle. Asymmetric distribution of two regulatory proteins in the early embryo helps create these timing differences, Rivers et al. show. Different cell types often differ in cell cycle length. Take AB and P1, the fi rst two cells of a worm embryo. AB completes its cycle about two minutes sooner than does P1. Researchers knew that Par proteins, which help set up the embryo’s polarity, are also responsible for unequal cell cycle times. What they didn’t know was how. Rivers et al. tested whether two key proteins that control the cell cycle, cyclin E and CDC-25.1, were involved. AB and P1 harbored equal amounts of cyclin E, indicating it wasn’t responsible for the timing difference. But the levels of CDC-25.1 are higher in the AB cell’s nucleus, and the protein builds up faster there, suggesting it drives the asynchrony. But what causes CDC-25.1 to accumulate in only one cell? One candidate was the polo-like kinase PLK-1, which helps the human counterpart of CDC-25.1 home in on the nucleus. Rivers et al. found that at the one-celled stage, PLK-1 amasses at the anterior end, which becomes AB after the fi rst cell division. In turn, Par proteins seem to help set up the PLK-1 asymmetry through two other proteins, which control protein degradation. These two proteins might spur the breakdown of an unidentifi ed inhibitor of PLK-1. Rivers, D.M., et al. 2008. J. Cell Biol. 180:877–885. Cells’ puncture repair kit A cell with a torn or perforated membrane has to close the breach fast. To heal wounds infl icted by bacteria, cells rely on endocytosis, Idone et al. show. An injury or even a workout at the gym can tear the plasma membranes of our cells. Earlier work showed that a wounded cell makes repairs through exocytosis, extruding lysosomes whose membranes help close the rip. But this mechanism alone can’t explain how cells heal all injuries. Some bacterial toxins and defensive proteins such as the complement system embed themselves in the membrane, forming a pore that can’t be closed by exocytosis. Idone et al. wanted to nail down how cells mend these types of perforations. The team exposed cells to Streptococcus toxin that bores into the plasma membrane. Repairs were quick—the membranes resealed in less than 30 seconds. Cells wouldn’t have time to disassemble the pores in that time, ruling out one possible mechanism. The team also discounted the possibility that injuryinduced blebs on the cell membrane somehow dislodge the pores—cells still healed when the team blocked blebbing. A third possibility is that cells use endocytosis to remove the pores from the membrane. To test the idea, Idone et al. followed labeled pores that were stuck in the membrane. Within a few seconds, endosomes carrying tagged toxin began showing up inside the cells. The results indicate that injury stimulates the formation of endosomes that engulf pores that have penetrated the membrane. The team also discovered that cells use the same method to excise membrane abrasions.