ON THE COVER
An Airyscan confocal image of a HeLa cell 8 hours after infection with vaccinia virus shows that during its egress the virus (purple) on the plasma membrane recruits SEPT7 (green). The virus appears white where it overlaps with SEPT7 Image © Pfanzelter et al., 2018.
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People & Ideas
Verlhac discusses new work from Burdyniuk et al. demonstrating how F-actin coordinates the capture of chromosomes by microtubules in oocytes.
Verlhac and Reggiori introduce work from Mostofa et al. that describes a role for the CLIP and cohibin complexes in repositioning ribosomal DNA during the process of nucleophagy.
Sung and Weaver discuss new work from Kriebel et al. showing how extracellular vesicles generate and sustain chemotactic signals.
Hoefig and Heissmeyer review how microRNAs, long noncoding RNAs, RNA-binding proteins, and ubiquitin-modifying enzymes regulate T helper cell differentiation downstream of transcription.
Matsui et al. identify YKT6 as a novel autophagosomal SNARE protein. YKT6 is required for autophagosome–lysosome fusion independently of STX17, a known autophagosomal SNARE.
Correlative light electron microscopy reveals microtubule assembly near most kinetochores at the onset of mitosis in human cells. Conversion of the initially lateral interactions between these microtubules and kinetochores into end-on attachments is facilitated by the kinesin CenpE. This work suggests that kinetochore fibers predominately form via capture of locally nucleated noncentrosomal microtubules.
An actin network moves chromosomes to the cortex of oocytes during asymmetric division. Burdyniuk et al. show that in starfish oocytes actin is nucleated around chromosomes in a RanGTP- and Arp2/3-dependent manner. These F-actin “patches” coordinate chromosome capture in the large oocyte by preventing the formation of premature kinetochore–microtubule attachments.
Nutrient starvation or inactivation of TORC1 induces separation of rDNA and nucleolar proteins in yeast. Mostofa et al. report that the rDNA tethering CLIP–cohibin system repositions nucleolar proteins to sites proximal to the nuclear–vacuolar junction (NVJ), where micronucleophagy occurs, whereas rDNA moves to regions distal to the NVJ.
Microtubules grow by the addition of bent guanosine triphosphate tubulin to the tips of curved protofilaments
How microtubules (MTs) grow during the addition of guanosine triphosphate (GTP) tubulin is not clear. McIntosh et al. now show that MTs elongating either in vivo or in vitro end in bent protofilaments that curve out from the microtubule axis, suggesting that GTP-tubulin is bent in solution and must straighten to join the MT wall.
Myosin VI and branched actin filaments mediate membrane constriction and fission of melanosomal tubule carriers
Pinching the neck of a budding tubule or vesicle requires mechanical forces. Ripoll et al. show that myosin VI, together with branched actin filaments, constricts the membrane of tubular carriers released from melanosomes, which allows for the export of components from melanosomes and promotes melanosome homeostasis, maturation, and transfer to keratinocytes.
Endosomal TLR3, TLR7, and TLR8 control neuronal morphology through different transcriptional programs
Hung et al. combine in vitro neuronal cultures, in utero electroporation, and transcriptomic profiling to show that the activation of TLR8, TLR7, or TLR3 results in dendritic shortening and that TLR7 and TLR3 but not TLR8 also control axonal growth. In-depth transcriptomic analyses show that TLRs use different downstream pathways to control neuronal morphology despite signaling through the same adapter, MYD88.
Atg2, Atg18, and Atg9 are important for autophagy, but their precise functions are unclear. Gómez-Sánchez et al. study Atg2 mutants unable to bind to Atg9 and show that the interaction with Atg9 confines Atg2 to the extremities of the expanding phagophore and that the assembly of the Atg9–Atg2–Atg18 complex plays a role in establishing phagophore–endoplasmic reticulum contact sites.
GATOR1-dependent recruitment of FLCN–FNIP to lysosomes coordinates Rag GTPase heterodimer nucleotide status in response to amino acids
A large number of lysosome-localized proteins control mTORC1 signaling. Rag guanosine triphosphatase (GTPase) heterodimers play a central role in this pathway by recruiting mTORC1 to lysosomes. Meng and Ferguson reveal how folliculin, a tumor suppressor, coordinates nucleotide states within Rag GTPase heterodimers.
Among ERα-positive breast cancers, approximately half fail to respond to endocrine therapy, and the causes of this resistance are unknown. Sampayo et al. show that fibronectin (FN) influences the trafficking of ERα-positive vesicles. FN promotes ERα localization in Rab11+ vesicles, rescues ERα from lysosomal degradation, and reinforces ERα trafficking to the nucleus and transcriptional activity in tumor cells.
CCL25, CXCL10, and Mn2+ induce three distinct active conformations of integrin α4β7, which have selective high affinity for either MAdCAM-1, VCAM-1, or nonselective high affinity for both ligands. Via this mechanism, integrin α4β7 adopts different active conformations to switch its ligand-binding specificity.
Epithelial and endothelial barriers exhibit heterotypic properties in distinct tissue types that are defined and controlled to a great extent by cytoskeleton dynamics. Hilfenhaus et al. highlight the critical role of the cytoskeletal regulator Vav3 in barrier function and heterogeneity of the endothelium.
Lee et al. examine the dynamics of membrane proteins within the ciliary membrane using quantum dots and 2P Super FRAP. They show that ciliary membrane proteins diffuse rapidly within highly fluid local membrane domains delimited by actin filaments.
The connecting cilium (CC) of photoreceptor cells is considered analogous to the primary cilium transition zone (TZ). Dharmat et al. identify two subzones within the CC: the TZ-like posterior CC and a novel photoreceptor-specific zone in the distal CC, which is maintained by the retinal ciliopathy gene SPATA7 and other photoreceptor-specific ciliary proteins.
The IFT-B complex powered by kinesin-II is believed to be responsible for anterograde ciliary protein trafficking. Funabashi et al. identify composite interactions of the kinesin-II heterotrimer KIF3A–KIF3B–KAP3 with the IFT-B–connecting tetramer IFT38–IFT52–IFT57–IFT88 and show that their interaction is crucial for ciliogenesis.
Messenger et al. show that exosome secretion in cancer cells is Ca2+-stimulated and dependent on Ca2+-bound Munc13-4. Munc13-4, a late endosome priming factor, acts via a Rab11-dependent pathway to prepare multivesicular endosomes for exocytosis. These results indicate that Munc13-4 plays a central role in exosome release in cancer cells.
Kriebel et al. show that Dictyostelium cells release extracellular vesicles (EVs) that not only contain the chemoattractant cAMP but also actively synthesize and release cAMP to promote chemotaxis. They show that the EV release of cAMP is mediated by the ABCC8 transporter.
Septins play important roles in many cellular processes. Pfanzelter et al. show that septins suppress the release of vaccinia virus from infected cells by trapping virions on the plasma membrane. This antiviral effect is overcome by dynamin and formin-mediated actin polymerization.
Bending et al. establish a new tool, Timer of cell kinetics and activity (Tocky), revealing the temporal dynamics of cellular activation and differentiation in vivo. The tool analyzes the temporal sequence of molecular processes during cellular differentiation and can classify cells based on the frequency they receive signaling events in vivo.
Casey et al. integrate epigenomic, transcriptomic, and proteomic profiling of primary basal and luminal mammary cells to identify master epigenetic regulators of the mammary epithelium and uncover stem and progenitor cell vulnerabilities. They develop a pipeline to identify drugs that abrogate progenitor cell activity in normal and high-risk breast cancer patient samples in vitro and in vivo.