Lysosomes for lunch

I f an intracellular parasite is too successful at hiding itself, it can end up starving. Toxoplasma gondii gets around this potential problem by munching nutrient-fi lled host lysosomes, say Isabelle Coppens and colleagues. T. gondii has an extraordinary mechanism for creating a parasitophorous vacuole (PV) around itself—it motors into a host mammalian cell and uses a ring-shaped moving junction to exclude almost all host-derived proteins from the nascent PV membrane. But this leaves the parasite responsible for importing all nutrients including, as Coppens and Joiner found previously, cholesterol. The group therefore looked at whether endocytosed cholesterol found its way to the PV. They found that it did, and that a wholesale rearrangement of the cytoskeleton was involved. Host microtubule-organizing centers (MTOCs) detached from the nucleus and reattached to the PV. Endolysosomes followed them, clustering around the PV. Finally, the microtubules nucleated by MTOCs surrounded and poked into the PV. But " the invagination is not a V like you would get from poking a balloon, " says Coppens. A parasite protein called GRA7 forms a collar around the invagination (which can be over 1-μm deep) that keeps it narrow. In most of the invaginations, a central micro-tubule allows host membranous compartments to be drawn inside. These compartments are eventually surrounded by PV-derived membrane as they are taken into the PV. The ingested lysosomes stay intact and thus do not spill their digestive contents. This reorganization of the cytoskeleton keeps the parasite fed. Further experiments will help determine whether the parasite also makes attractants to lure lysosomes into the PV's mouth. A urélien Roux, Pietro de Camilli, and colleagues (Yale University, New Haven, CT) report the best evidence yet that dynamin uses mechanochemical activity— specifi cally a twisting action—to pinch off endocytic vesicles. Dynamin was, early on, localized to the collar around the neck of forming endocytic vesicles. This suggested that dynamin may use the energy of GTP hydrolysis to directly pinch a membranous neck. Indeed, dynamin could tubulate lipids and break apart the tubules in vitro, although later it seemed that the breaking apart was happening as the samples dried on EM grids. had come up with a " regulatory GTPase " model: that dynamin was active not as it hydrolyzed GTP but in its GTP-bound form, which recruited other proteins to do the pinching. This theory was controversial, and now the Yale group has more evidence for the …