Letters

During mitosis, store-operated Ca²⁺ entry (SOCE) is suppressed. Translocation of the ER Ca²⁺ sensor STIM1 to the plasma membrane is critical to SOCE activation, but in mitotic cells STIM1 is phosphorylated and fails to rearrange into near-plasma membrane puncta. Mutation of mitosis-specific phosphorylation sites rescues mitotic SOCE.

IFT20, known to control intraflagellar transport during cilia biogenesis, is also expressed in lymphoid and myeloid non-ciliated cells. IFT20 is localized to the secretory pathway in T-lymphocytes and translocates to the immune synapse on antigen engagement to modulate the recycling of T-cell receptors.

Under prolonged ER stress, expression of the unfolded protein response effector CHOP becomes cytotoxic. Toll-like receptor engagement activates TRIF signalling to inhibit the translational activation of the UPR effector ATF4 and thus suppresses CHOP-associated cell death and organ dysfunction in mice.

The Slit2 receptor Robo4 is known to maintain vascular permeability. Robo 4 prevents the formation of endothelial cell protrusions through a complex with paxillin and Arf–GAPs, which inhibits the GTPase Arf6a and thus leads to Rac activation.

Two inhibitors of death receptor-associated apoptosis, cellular c-FLIP and viral v-FLIP prevents LC3 processing by Atg3 and thus repress the autophagic cell death that follows mTOR inhibition. Short peptides derived from FLIP can prevent Atg3–FLIP interaction without affecting Atg3–LC3, restoring cell death.

The γ-secretase complex is responsible for the generation of amyloid β-peptide, the main component of Alzheimer's disease associated plaques. A proteomic analysis yielded secretory pathway components and membrane-associated tetraspannin microdomains as interactors and regulators of the γ-secretase complex.

Substrates of plant metacaspases, cystein proteases involved in plant programmed cell death (PCD), have been so far unknown. Metacaspase II is now shown to cleave the splicing regulator Tudor staphylococcal nuclease (TSN) during developmental and stress-induced PCD, an activity shared with caspase-3 during apoptosis in animals.

The anaphase-promoting complex (APC/C), a ubiquitin ligase regulating mitotic progression, is a target for spindle assembly checkpoint. UBE2S, an ubiquitin-conjugating enzyme, is identified as a novel factor that elongates ubiquitin chains and promotes APC/C substrate degradation following release from the spindle assembly checkpoint.

Parkin, an ubiquitin ligase whose mutations are associated with early development of Parkinson's disease, possesses a RING domain, suggesting it can modulate transcription. Parkin represses the expression of p53 both in fibroblasts and mice brains, independently of its ligase activity, and patient brain samples exhibit high levels of p53.

Tip60 acetylation of ATM kinase is necessary for DNA double-strand break repair and cancer suppression. Tip60 is recruited to breaks by histoneH3 trimethylated on lysine 9 and the Mre11/Rad50/Nbs1 damage response complex, activating its acetyltransferase activity.

Inactivation of the tumour suppressor PTEN leads to enlarged neuronal soma. The actin-based motor myosin Va is shown to control soma size by transporting PTEN in a manner dependent on PTEN phosphorylation by CK2 and/or GSK3.

Fluid flow towards the leading edge has been suggested to have a role in cell motility, but the existence of fluid flow had not been demonstrated directly. Insertion of quantum dots into the lamellipodia of fish keratinocytes now reveals a forward-directed fluid flow that is dependent on myosin II activity.

BBF2H7, a transcription factor activated by ER stress, is shown to be essential for chondrogenesis. Mice lacking BBF2H7 show severe chondrodysplasia and null chondrocytes have defects in secreting cartilage matrix proteins. BBF2H7 induces the expression of Sec23a, which is required for ER to Golgi transport, and rescues the secretion of cartilage matrix proteins in null cells.

Listeria monocytogenes spreads by membrane protrusions produced by actin 'comet tails'. The secreted Listeria protein InclC binds the mammalian adaptor protein Tuba to prevent activation of the actin regulator N-WASP2, which causes disruption of apical junctions and protrusion formation.

The planar cell polarity (PCP) effector Fuz had not been studied in mice. Due to disrupted ciliogenesis, Fuz mutant mice show neural tube and skeletal defects. Fuz regulates trafficking of membrane cargoes to cilia through its interaction with a GTPase of the Rab family.

The transcription factor OASIS was previously implicated in the ER stress response. BMP2 signalling, which is required for bone formation, induces OASIS expression and activation. Mice lacking OASIS show severe defects in bone formation and in response to BMP2 signalling. OASIS directly induces expression of Col1a1, a component of type 1 collagen.

Autophagy degrades invading bacteria in the cytoplasm, however, Listeria monocytogenes can efficiently escape autophagy. The Listeria protein ActA recruits the actin-regulators Arp2/3 and Ena/VASP to disguise it from autophagic recognition. Tagging PolyQ-containing, aggregate-prone proteins or a Golgi-membrane protein with ActA also prevents their autophagy-mediated degradation.

Cells undergoing normal or premature ageing show several global defects in chromatin. Components of the NURD chromatin remodelling complex, such as histone chaperones, are now shown to be lost in cells from patients with a premature aging disorder and in normally aged cells. Conversely, depleting NURD subunits and Hdac1 recapitulates the chromatin defects seen in aged cells.

Inhibition of the CDC25A phosphatase is critical for activation of the DNA damage-induced G2/M checkpoint. The DNA damage-activated kinase CHK1 phosphorylates the NIMA-related kinase NEK11, which in turn phosphorylates CDC25A to induce its degradation.

The brassinosteroid (BR) signalling pathway results in the activation of BZR transcription factors to control plant development. The complete pathway is established here, by showing that BR induces the BSU1 phosphatase-dependent inactivation of the GSK3-like kinase BIN2, thereby leading to accumulation of unphosphorylated BZR factors in the nucleus.