People & Ideas
Sharma and Dwivedi highlight recent work from Wang et al. describing two GTPases that function directly as dynein adaptors for retrograde transport.
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.
Jost and Waters review best practices for validation of quantitative microscopy methods and strategies to avoid unconscious bias in imaging experiments.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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 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.
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.
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.
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.
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.
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.