People & Ideas
Kulkarni and Maday preview studies from Cheng et al. and Yap et al. characterizing the organization of the endolysosomal system in neurons.
Zaidel-Bar introduces work by Jones et al. demonstrating how adhesion is regulated during the cell cycle by CDK1.
Sivakumar and Kurpios review how transcription regulates cell shape changes during organ development in embryogenesis.
The mechanism by which the Drosophila chromokinesin NOD promotes chromosome congression is unknown. Ye et al. demonstrate that NOD generates force by two mechanisms: plus end–directed motility and microtubule plus-tip tracking via interaction with EB1 through a newly identified motif.
Nde1 plays a role in recruitment of cytoplasmic dynein to cargo. This study finds that Cdk1 phosphorylation of Nde1 enhances its recruitment by CENP-F. This interaction controls Nde1 and, in turn, dynein levels at the G2 nuclear envelope and mitotic kinetochores from prophase through anaphase.
Intermediate filaments control collective migration by restricting traction forces and sustaining cell–cell contacts
Using an in vitro wound healing assay, De Pascalis et al. show that intermediate filaments (IFs) participate in the dynamics of the acto-myosin network and its association with adhesions in astrocytes during collective migration. Glial IFs control the distribution of forces and the interactions between neighboring cells, ultimately determining the speed and direction of collective migration.
In contrast to vertebrates, adult Drosophila melanogaster have an open cardiovascular system. However, Thuma et al. find that in late pupation, hemolymph flows through Drosophila wing veins, providing a unique genetic and live-imaging opportunity to investigate the mechanisms driving immune cell extravasation from vessels to wounds and reveal new roles for Tre1 and Rho signaling in this process.
Spindle rotation in human cells is reliant on a MARK2-mediated equatorial spindle-centering mechanism
Unlike man-made wheels that are centered and rotated via an axle, the mitotic spindle of a human cell is rotated by external cortical pulling mechanisms. Zulkipli et al. identify MARK2’s role in equatorial spindle centering and astral microtubule length, which in turn control spindle rotation.
Src activation by Chk1 promotes actin patch formation and prevents chromatin bridge breakage in cytokinesis
When chromatin bridges form in cytokinesis, cells display actin patches at the intercellular canal. Dandoulaki et al. show that Chk1 phosphorylates Src at serine 51 to fully induce Src catalytic activity. In turn, phosphorylated Src-S51 promotes the formation of actin patches and prevents chromatin bridges from breaking.
Mitochondrial β-barrel proteins are imported from the cytosol into the organelle. Jores et al. provide new insights into the early events of this process by describing an array of cytosolic chaperones and cochaperones that associate with newly synthesized β-barrel proteins and assure their optimal biogenesis.
Phosphatidic acid (PA) lipids have a dual role as building blocks for membrane biogenesis and as active signaling molecules. This study establishes the molecular details of selective PA recognition by the transcriptional regulator Opi1 from baker’s yeast.
Cheng et al. combine quantitative immunoelectron microscopy and light imaging microscopy to comprehensively analyze LAMP1 subcellular distribution in neurons. The data show that a significant portion of LAMP1-positive organelles are not degradative, illustrating the need for additional lysosomal and endocytic markers to define endolysosomal compartments in the nervous system.
Yap et al. show that in neurons, degradative lysosomes are clustered in proximal dendrites and in the soma, leading to a steep spatial gradient of degradative capacity along dendrites. Terminal degradation of dendritic cargos requires Rab7-dependent transport to the soma, suggesting that proteostasis is spatially regulated in neurons.
A NUMB–EFA6B–ARF6 recycling route controls apically restricted cell protrusions and mesenchymal motility
How the endocytic protein NUMB modulates mesenchymal migration is unclear. Zobel et al. show that NUMB limits the formation of apically restricted, actin-based protrusions called circular dorsal ruffles (CDRs). NUMB activates the ARF6 guanine nucleotide exchange factor EFA6B and controls the trafficking rate of ARF6-dependent cargos relevant for CDR formation, such as RAC1, and negatively regulates HGF-induced cell migration and invasion.
ARHGAP35 encoding the RhoGAP p190A is one of the most frequently mutated genes in human cancer, which suggests that p190A may have a tumor-suppressive function. Frank et al. demonstrate that p190A and its paralog p190B mediate contact inhibition of epithelial cell proliferation by repressing YAP-mediated gene transcription.
Adherent cells round up before dividing, but how this is linked to the cell cycle is unclear. Jones et al. demonstrate that CDK1 promotes adhesion complex formation and increases cell adhesion area from G1 to S phase. Subsequently, inhibitory phosphorylation of CDK1 by cyclin B1 triggers adhesion complex disassembly during G2 in preparation for mitosis.
Desmosomal mutations result in potentially deadly cardiocutaneous disease caused by electrical conduction defects and disruption of gap junctions. Kam et al. demonstrate a mechanism whereby loss of the intermediate filament anchoring protein desmoplakin stimulates Cx43 turnover by increasing K-Ras expression, marking Cx43 for lysosomal degradation through ERK1/2 phosphorylation.
Programmed cell death is a critical process in sculpting the developing nervous system, but the underlying signaling mechanisms remain poorly defined. Donnelly et al. demonstrate a non-canonical function for the neurotrophic factor receptor Ret in p75-mediated apoptosis in sympathetic neurons.
Actin polymerization is important to generate primary cilia. Drummond et al. show that upstream actin regulators are necessary for this process by controlling aPKC and Src kinase activity to promote Hedgehog signaling and restrict primary cilia.
Shedding of CD16 disassembles the NK cell immune synapse and boosts serial engagement of target cells
A long-standing unknown is how an immune synapse disassembles. In this study, Srpan et al. show that shedding of CD16 promotes the detachment of NK cells from target cells to aid serial engagement of multiple targets and to sustain NK cell viability.
Drosophila melanogaster neural stem cells (neuroblasts) divide asymmetrically by differentially segregating protein determinants into their daughter cells. Wissel et al. use time-resolved transcriptional profiling to identify a v-ATPase/Notch regulatory loop that acts in multiple stem cell lineages both during nervous system development and in the adult gut.
Genome-edited human stem cells expressing fluorescently labeled endocytic markers allow quantitative analysis of clathrin-mediated endocytosis during differentiation
Dambournet et al. generate genome-edited human embryonic stem cells (hESCs) labeled with endocytic markers. They comparatively and quantitatively analyze the dynamics of clathrin-mediated endocytosis during differentiation through live-cell imaging and platinum replica EM in hESCs and their isogenic progeny.