People & Ideas
Perez-Vale and Peifer highlight new work from Gamblin et al. revealing how apical–basal polarity is controlled by Yurt oligomerization.
Venkei and Yamashita summarize recent advances in our understanding of asymmetric stem cell division in tissue homeostasis.
Xia et al. show how force probes and cytoskeletal stress can induce nucleus-specific rupture. Rupture correlates with nuclear curvature and is promoted by low lamin A, high actomyosin stress, and stiff ECM. Rupture leads to cytoplasmic mislocalization of DNA repair factors.
Alford and Brandman quantify the ability of the Hsp90 chaperone system to fold its client proteins and describe how loss of this functionality affects the heat shock response. They find that the heat shock response responds to diverse defects in protein quality by monitoring the state of multiple chaperone systems independently.
Morita et al. identify the endoplasmic reticulum multispanning membrane protein TMEM41B as a factor required for autophagosome formation. TMEM41B interacts physically and functionally with VMP1, a structurally related autophagy protein.
Irradiation temporarily arrests tissue regeneration. Volin et al. show that the ability of stem cells to regain regeneration relies on the resistance of their niche-supporting cells to apoptosis. This resistance is mediated by microRNAs that prevent apoptosis induction.
Control of epithelial cell death is crucial to maintaining tissue integrity. Gagnoux-Palacios et al. show that cell polarity and adherens junction formation prevent proapoptotic signals emanating from the Fas death receptor. Therefore, Fas-dependent cell death contributes to the elimination of nonpolarized or nonadherent cells from human epithelia.
The ability of the polarity protein Yurt to bind to Crumbs and to maintain epithelial cell polarity depends on its oligomerization. aPKC-dependent phosphorylation dismantles the Yurt oligomer to maintain Crumbs function and apical domain integrity in polarized epithelial cells.
Legionella pneumophila enters cells in a vacuole derived from the plasma membrane, which then sequesters vesicles from the ER in order to support parasite growth and immune evasion. Arasaki et al. now reveal that the Legionella effector DrrA recruits components of the exocyst to promote tethering of host vesicles with the LCV.
Condon et al. use lattice light-sheet microscopy to analyze live macrophages and define a new model of macropinosome formation and closure through tent pole ruffles. The ruffles, which are enhanced by LPS and regulated by Rab13, are erected and supported by F-actin tent poles that cross over and twist to constrict the forming macropinosomes.
The evolutionarily divergent class of kinetoplastid organisms has a set of unconventional kinetochore proteins that drive chromosome segregation, but it is unclear which components interact with spindle microtubules. Llauró et al. now identify KKT4 as the first microtubule-binding kinetochore protein in Trypanosoma brucei, a major human pathogenic parasite.
Cyclin B1 and its interaction with CDK1 are thought to be critical for meiosis I progression in oocytes. However, using oocyte-specific conditional knockouts, Li et al. show that Cyclin B2 activity can compensate for Cyclin B1 to trigger meiosis resumption.
Nuclear speckles (NSs) store splicing factors. Wang et al. show that many naturally intronless mRNAs associate with NSs and that speckle association enhances their export by facilitating TREX recruitment, suggesting that trafficking to NSs could be an important quality control step in intronless mRNA export.
Chromosome number is highly regulated in cells, while genome instability is associated with cancer. Resende et al. show that induction of chromosome imbalance in stem cells of the fruit fly adult gut leads to tissue pathology highly reminiscent of early stages of human tumor development.
Mallik et al. identify Xrp1 as a nuclear chromatin-binding protein involved in gene expression regulation that mediates phenotypes induced by loss of function of cabeza (caz), the Drosophila melanogaster orthologue of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) protein FUS. Knockdown of Xrp1 in motor neurons rescues phenotypes induced by ALS-mutant FUS.
White et al. find that intracellular pH regulates the stability of β-catenin, the Wnt signaling molecule that controls cell polarity, adhesion, and differentiation. A conserved histidine residue in β-catenin mediates pH-dependent binding to the E3 ligase β-TrCP for degradation, and a cancer-associated mutation that bypasses this pH-sensitive regulation induces ectopic tumors in the Drosophila eye.
Clearance of apoptotic cells is essential for tissue maintenance and initiated by recognition of “eat-me” ligands on the dead cells. Using a simplified cellular reconstitution system, Williamson and Vale report that the Drosophila melanogaster engulfment receptor Draper (CED-1/Megf10) is triggered in a manner similar to mammalian immune receptors.
The retinal ribbon synapse is important for the processing of visual information. Hagiwara et al. show that the active zone proteins CAST and ELKS perform both redundant and unique functions in photoreceptors to promote the maturation, maintenance, and activity of ribbon synapses.
Synapse formation relies on the coordination of dynamic pre- and postsynaptic structures during brain development. Liu et al. reveal that presynaptic terminal maturation of mossy fiber axons is retrogradely regulated by postsynaptic scaffold protein Lnx1 via stabilizing EphB receptor kinases.
Mapping 3D genome organization relative to nuclear compartments using TSA-Seq as a cytological ruler
Chen et al. present TSA-Seq, a new mapping method that measures cytological distances relative to spatially distinct nuclear subcompartments. From novel nuclear organization maps of human cells, they identify transcription hot zones of high gene density that are near nuclear speckles and enriched in highly expressed genes, housekeeping genes, and genes with low transcriptional pausing.