Research articles

Integrin internalization through the endosomal pathway can lead either to recycling back to the surface or to lysosomal degradation. Faessler and colleagues now show that, following internalization, β1 integrins are bound by sorting nexin 17 in early endosomes to prevent integrin degradation in lysosomes and to promote surface recycling.

Wedlich-Söldner and colleagues characterize the localization of plasma membrane proteins in Saccharomyces cerevisiae by total internal reflection microscopy and deconvolution. Their data reveal a self-organization of proteins into patterns and demonstrate that association of the arginine transporter Can1 with its membrane domain is important for its function.

MCL-1 is an anti-apoptotic BCL-2 family member and is frequently upregulated in cancer, but the mechanism by which it promotes cell survival has been elusive. Opferman and colleagues provide insight into this process by showing that MCL-1 exists in different forms with discrete localizations and functions. MCL-1 variants targeted to the outer mitochondrial membrane antagonize BAX and BAK activation, whereas an N-terminally truncated isoform localizes to the mitochondrial matrix and regulates mitochondrial metabolism.

Clathrin-mediated endocytosis requires the generation of membrane curvature and subsequent formation of clathrin-coated vesicles. Using a cell-free system, Dannhauser and Ungewickell show that clathrin polymerization is capable of inducing membrane deformation and generating spherical vesicles.

Iavarone, Lasorella and colleagues develop genetic mouse models to study the roles of inhibitor of DNA-binding (Id) proteins in neural stem-cell maintenance. They show that Id proteins promote neural stem-cell adhesion to their niche by driving the transcriptional repression of Rap1GAP, thereby maintaining the activity of the Rap1 GTPase, a known regulator of integrin adhesion.

Transcription-factor-directed reprogramming of somatic cells is inefficient but can be enhanced by the addition of enzymes that modulate chromatin modifications. Zhang and colleagues report that the Kdm2b H3K36me2 demethylase promotes reprogramming through its enzymatic activity and independently of its role in senescence, by enhancing the transcription of genes known to be activated early during the process, including cadherin.

The lipid content of the plasma membrane is dynamically regulated to maintain cellular homeostasis, but the molecular links between membrane stress and sphingolipid synthesis have remained elusive. Walther, Loewith and colleagues report that membrane stretching causes redistribution of Slm proteins, which then promote sphingolipid synthesis through activation of the TORC2–Ypk signalling pathway.

Schweisguth and colleagues have uncovered a Notch-independent role for the E3 ubiquitin ligase Neuralized that entails disrupting existing epithelial polarity and cell junctions to allow cell movements that are critical during Drosophila development. They show that Neuralized’s effect on polarity is normally antagonized by Bearded, which is a known target of the Snail repressor, a transcription factor involved in polarity regulation at gastrulation. Targets for Snail that are relevant in this process have, until now, been elusive.

Repair of double-strand breaks (DSBs) by homologous recombination is thought to involve the movement of damaged chromosomes to facilitate pairing of homologues. Rothstein and colleagues have now followed the movement of damaged loci in diploid yeast by time-lapse microscopy, revealing the dynamics of damage-induced movement and the requirement for repair proteins in this process.

Repair of double-strand breaks by homologous recombination is thought to involve the movement of damaged chromosomes to facilitate pairing of homologues. Gasser and colleagues have now followed the movement of damaged loci in haploid yeast using time-lapse microscopy, revealing the dynamics of damage-induced movement and the requirement for recombination proteins in this process.

Clathrin-mediated endocytosis requires the coordinated spatial and temporal recruitment of adaptor, sorting and cargo proteins. Traub and colleagues investigate this process during zebrafish development and report that the AP-2 adaptor protein complex has a key, early role in clathrin-coated bud formation. Fcho1/2, though necessary for proper development, seems to act downstream of AP-2.

The transcription factor SPEECHLESS (SPCH) is necessary for establishing the stomatal lineage in plants, but the signalling pathways that control this process are not fully understood. Russinova and colleagues report that brassinosteroid signalling regulates stomatal development by inhibiting BIN2-mediated phosphorylation of SPCH.

Luschnig and colleagues show that the oncogene Src instructs changes in cell shape that mediate tracheal tube elongation in Drosophila, and implicate E-Cadherin recycling at adherens junctions in this process.

The ATM motif was previously shown to phosphorylate the BH3-only BID protein, a pro-apoptotic member of the BCL2 family. Using transgenic mice expressing a phosphodefective BID, Gross and colleagues find that the ATM effect on BID prevents its translocation to the mitochondria, where the effects of BID on ROS would trigger haematopoietic stem cells to exit quiescence.

Beitel and colleagues show that the proto-oncogene Src regulates tracheal tube dimensions in Drosophila by directing anisotropic apical membrane growth in concert with the formin dDaam.

D’Adda di Fagagna and colleagues observe that, after genotoxic treatment of cells and mice, unrepaired DNA-damage foci and DNA-damage signalling persist at telomeres. They show that introducing the telomeric protein TRF2 near a double-strand break elsewhere on the chromosomes prevents repair. Unrepaired foci are also observed at telomeres of ageing animals, suggesting a role for TRF2 in senescence establishment.

Seamless tubes are found in Drosophila tracheal terminal cells, but it is still unclear how they grow. Ghabrial and colleagues find that the small GTPase Rab35, and its apically localized GAP, Whacked, direct tube shape and growth. They also highlight a role for dynein in this process.

Haematopoietic progenitor activity in the Drosophila lymph gland can respond to stress. Banerjee and colleagues show that systemic insulin and nutritional signals maintain these progenitors by modulating Wingless-dependent pathways.

Yang and colleagues delineate a pathway that controls cell migration in 3D environments following Twist1-mediated epithelial-to-mesenchymal transition. They show that Twist1 represses the let-7i microRNA, leading to upregulation of the RAC1-activating factors NEDD9 and DOCK3, and inducing mesenchymal-mode motility and tumour invasion in vivo.

Entry into the cilium is restricted by a network of proteins at its base. Verhey and colleagues now show that nucleoporins, which localize to the nuclear envelope and regulate nuclear–cytoplasmic traffic, are also present at the cilium base, where they form a size-dependent exclusion barrier.