Cell death

Nucleotides released by apoptotic cells act as a find-me signal to promote phagocytic clearance Elliott, M. R. et al. Nature 461, 282–286 (2009)

Apoptotic cells are promptly removed by phagocytosis because their accumulation can lead to autoimmunity and chronic inflammatory diseases. A new study reveals that apoptotic cells secrete nucleotides to attract motile phagocytes. Cell-free supernatants from cultured apoptotic thymocytes attract phagocytic monocytes in vitro and in mice. Specifically, the nucleoside triphosphates ATP and UTP, which signal through the G protein-coupled purinergic receptor P2Y2, function as chemoattractants that are released from apoptotic cells. Silencing of P2Y2 in macrophages impairs cell migration in vitro in response to apoptotic supernatants, and a strong decrease in monocyte recruitment is observed in P2Y2-deficient mice. Thus, a clear relationship between nucleotide 'find-me' signals and in vivo apoptotic cell clearance has been established.

Cell death

Oxidant-induced apoptosis is mediated by oxidation of the actin-regulatory protein cofilin Klamt, F. et al. Nature Cell Biol. 6 Sep 2009 (doi: 10.1038/ncb1968)

Oxidants can induce cellular damage and death, but how protein oxidation leads to apoptotic cell death remains unclear. Klamt et al. have identified 21 proteins that are oxidized in human cells after treatment with taurine chloramine (TnCl) — an oxidant that causes cell death only through apoptosis. TnCl-induced oxidation of Cys and Met in the actin-regulatory protein cofilin, known to have a role in apoptosis, impairs its ability to bind to actin and results in its translocation from the cytosol to mitochondria. Oxidized cofilin induces the opening of the mitochondrial permeability transition pore (PTP), leading to mitochondrial swelling and the release of cytochrome c — two features of mitochondria-driven apoptosis. Cofilin is the first protein that has been shown to stimulate the opening of the PTP depending on its state of oxidation. Whether cofilin interacts directly with PTP remains to be elucidated.

Cytoskeleton

Rab35 controls actin bundling by recruiting fascin as an effector protein Zhang, J. et al. Science 325, 1250–1254 (2009)

Cell migration, cytokinesis and cell integrity all depend on actin filaments being polymerized and assembled into higher order structures at specific locations. Zhang et al. show that RAB35, which controls intracellular vesicle trafficking, also positively affects actin cytoskeleton dynamics by binding to the actin-bundling protein fascin. Expression of dominant-negative RAB35 or silencing of endogenous Rab35 in Drosophila melanogaster results in defective mechanosensory bristles with disorganized actin filaments. In mammalian cells, overexpression of RAB35 induces the formation of filopodium-like protrusions in a fascin-dependent manner. Furthermore, targeting RAB35 to the mitochondrial membrane of cultured cells, where it is normally absent, leads to the relocation of fascin to the mitochondria and the assembly of actin filaments. This suggests that RAB35 recruits fascin to promote actin bundling.