Issues
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Cover Image
Cover Image
ON THE COVER
Electron micrograph image showing organization of sarcomeres in skeletal myofibers, including the triads formed by the juxtaposition of the sarcoplasmic reticulum and transverse tubules with adjacent mitochondria shown in blue. The I-bands, containing actin, and the A-bands, containing actin and myosin, are colored in red. Image © Oury et al., 2019. See page 1686. - PDF Icon PDF LinkTable of Contents
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People & Ideas
Gabriel Muhire Gihana: A candle loses nothing by lighting other candles
Gihana investigates how cells coordinate their shape and polarity with chromosome segregation.
Spotlights
Active RNA polymerase II curbs chromatin movement
Hochberg-Laufer and Shav-Tal discuss recent work from the Maeshima laboratory showing that chromatin mobility genome-wide is limited by active RNAPII transcription.
A CRACker of an adaptor connects dynein-mediated transport to calcium signaling
Sharma and Dwivedi highlight recent work from Wang et al. describing two GTPases that function directly as dynein adaptors for retrograde transport.
ATG9 raises the BAR for PI4P in autophagy
Shatz and Elazar discuss a recent study from Judith et al. demonstrating how ATG9A vesicles drive early autophagy.
Neurons regulate synaptic strength through homeostatic scaling of active zones
Cunningham and Littleton preview work from Goel et al. that describes a mechanism by which neurons regulate synaptic output after alterations in synapse size or active zone number.
Reviews
How cells fuse
Brukman et al. review cell–cell fusion mechanisms, focusing on the identity of the fusogens that mediate these processes and the regulation of their activities.
Designing a rigorous microscopy experiment: Validating methods and avoiding bias
Jost and Waters review best practices for validation of quantitative microscopy methods and strategies to avoid unconscious bias in imaging experiments.
Reports
Cell cycle– and genomic distance–dependent dynamics of a discrete chromosomal region
Ma et al. use the CRISPR-Sirius system to track the dynamics of genomic loci situated kilobases to megabases apart on a single chromosome throughout the cell cycle, providing insight into the compaction–relaxation dynamics of the interphase chromosome fiber concurrent with changes in the overall movements of loci in the 4D genome.
Yeast centrosome components form a noncanonical LINC complex at the nuclear envelope insertion site
How the nuclear envelope is remodeled to facilitate insertion of large protein complexes is poorly understood. Chen et al. use superresolution imaging with bimolecular fluorescence complementation to show that a novel noncanonical linker of nucleoskeleton and cytoskeleton (LINC) complex forms at sites of nuclear envelope fenestration in yeast.
Extramitochondrial cardiolipin suggests a novel function of mitochondria in spermatogenesis
The acrosome is a protease-rich organelle in sperm essential for fertilization but little is known about acrosome biogenesis. Ren et al. find that the mitochondrial lipid cardiolipin and some mitochondrial proteins translocate to the acrosome during spermatogenesis, suggesting that mitochondria directly contribute to the assembly of this sperm-specific organelle.
COPII vesicles contribute to autophagosomal membranes
The membrane dynamics underlying the biogenesis of autophagosomes, including the origin of the autophagosomal membrane, are still elusive. Shima et al. use a recently developed COPII vesicle–labeling system to show that COPII vesicles are a membrane source in autophagosome formation.
Articles
Single nucleosome imaging reveals loose genome chromatin networks via active RNA polymerase II
When a gene is activated, chromatin in the transcribed region is thought to be more open and dynamic. However, Nagashima et al. found that this is not necessarily the case—inhibition of transcription globally increases chromatin motion, revealing the existence of loose genome chromatin networks via transcriptional machinery.
Live imaging of marked chromosome regions reveals their dynamic resolution and compaction in mitosis
Eykelenboom et al. track marked chromosome regions in live imaging of human cells with high spatial and temporal resolution to shed light on mitotic chromosome resolution and compaction dynamics.
Cyclin B3 is required for metaphase to anaphase transition in oocyte meiosis I
Proper chromosome segregation during meiosis requires cyclins associated with cyclin-dependent kinases. Li et al. generate Ccnb3 mutant mice via CRISPR/Cas9 and identify a requirement for cyclin B3 in female meiosis I.
Translation factor mRNA granules direct protein synthetic capacity to regions of polarized growth
Pizzinga et al. show that mRNAs encoding a range of translation factors are localized to granules that get transported into the yeast daughter cell using the She2p/She3p machinery. This likely supports an intensification of protein synthetic activity to facilitate apical polarized growth.
Maturation-driven transport and AP-1–dependent recycling of a secretory cargo in the Golgi
The Golgi cisternal maturation model predicts that secretory cargo proteins should be continuously present within the cisternae while resident Golgi proteins come and go. Casler et al. verify this prediction by tracking the passage of a fluorescent secretory cargo through the yeast Golgi.
Visualization of secretory cargo transport within the Golgi apparatus
Kurokawa et al. visualize the transport of secretory cargo in the Golgi apparatus in living yeast cells. Cargo stays in the cisterna, whose property changes from cis to trans and further to the trans-Golgi network, but shows a dynamic behavior between the early and the late zones within the maturing cisterna.
CRACR2a is a calcium-activated dynein adaptor protein that regulates endocytic traffic
Transport of intracellular cargo generally requires coiled-coil adaptor proteins that connect cargo-bound receptors, usually GTPases, to dynein motor complexes. Wang et al. report that two Rab GTPases, CRACR2a and Rab45, contain coiled-coil domains and can directly act as dynein adaptors with CRACR2a–dynein participating in calcium-regulated endocytic trafficking.
ATG9A shapes the forming autophagosome through Arfaptin 2 and phosphatidylinositol 4-kinase IIIβ
ATG9A is essential during autophagosome biogenesis; however, the function of this multispanning membrane protein is not well defined. Judith et al. report that ATG9A vesicles deliver PI4KIIIβ to the autophagosome nucleation site to produce PI4P and initiate autophagosome formation.
Drosophila FGF cleavage is required for efficient intracellular sorting and intercellular dispersal
Bnl controls tracheal development in Drosophila, but it is unclear how this fibroblast growth factor is prepared for tissue-specific dispersal. Sohr et al. find that Furin1 cleaves Bnl in the Golgi, which polarizes its sorting to the basal surface of the source cells and determines its range of cytoneme-mediated intercellular dispersion, signaling, and branching morphogenesis.
Tks5 and Dynamin-2 enhance actin bundle rigidity in invadosomes to promote myoblast fusion
The actin cytoskeleton drives formation of membrane protrusions that promote cell–cell fusion. Chuang et al. now find that the invadosome scaffold protein Tks5 is required for myoblast fusion. Tks5 regulates the assembly of dynamin-2 around actin bundles, thus strengthening the stiffness of the invadosome to propel cell–cell fusion.
MACF1 links Rapsyn to microtubule- and actin-binding proteins to maintain neuromuscular synapses
Oury et al. show that the scaffolding protein MACF1 links Rapsyn, which binds acetylcholine receptors, to the microtubule- and actin-network at neuromuscular synapses. MACF1 thereby plays a role in synaptic maturation in mice, and mutations of MACF1 are associated with congenital myasthenia in humans.
Homeostatic scaling of active zone scaffolds maintains global synaptic strength
The mechanisms that stabilize synaptic strength are enigmatic. Goel et al. demonstrate that the abundance and nanostructure of scaffolds at presynaptic active zones are bidirectionally scaled to homeostatically calibrate global neurotransmitter release at the Drosophila melanogaster neuromuscular junction.
VE-PTP stabilizes VE-cadherin junctions and the endothelial barrier via a phosphatase-independent mechanism
Juettner et al. describe a novel phosphatase-activity–independent mechanism by which the phosphatase VE-PTP restricts endothelial permeability. VE-PTP functions as a scaffold that binds and inhibits the RhoGEF GEF-H1, limiting RhoA-dependent tension across VE-cadherin junctions and decreasing VE-cadherin internalization to stabilize adherens junctions and reduce endothelial permeability.
GPCR-independent activation of G proteins promotes apical cell constriction in vivo
This work provides direct evidence that heterotrimeric G proteins can be activated in vivo by a cytoplasmic factor instead of by a GPCR. Specifically, DAPLE, a nonreceptor protein bearing an evolutionarily conserved Gα-binding and -activating (GBA) motif, triggers apical cell constriction during neurulation in Xenopus laevis embryos via G protein–dependent signaling.