ON THE COVER
Getting together: Composite mosaic depicting the steps in the dance and interaction between mouse embryonic and trophoblast stem cells. The design is inspired by the rotational symmetry of stained-glass rose windows. The cells were stained to highlight β-catenin (red), F-actin (cyan or orange), and the nucleus (purple or blue). Image © Junyent et al., 2021 https://doi.org/10.1083/jcb.202005095
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New editorial board members
We are pleased to introduce the newest members of the JCB editorial board.
People & Ideas
Interviewing for a PI position—the pandemic way
JCB asks early career researchers to share their experience interviewing for academic faculty positions and becoming independent PIs during the COVID-19 pandemic.
Straightening up is required to nucleate new microtubules
Gardner highlights work from Ayukawa et al. that reveals that microtubule oligomer curvature, rather than length, is the limiting factor that slows the microtubule nucleation rate.
A dimmer switch for endosome-to–cell surface recycling
Seaman previews work from the Jia laboratory describing how MAPK signaling regulates endosomal protein sorting during stress.
Lose it to use it
Haddix and Rasband discuss work from Wang et al. describing how neuromuscular synapse elimination influences myelination.
The dynamic instability of actin filament barbed ends
Romet-Lemonne and Jégou discuss recent evidence that actin filaments can both grow and shrink in elongation-promoting conditions.
The cell biology of Parkinson’s disease
Panicker et al. summarize the functions of monogenic Parkinson’s disease genes and the major cell biological pathways that contribute to neurodegeneration.
Phase separation of Axin organizes the β-catenin destruction complex
Assembly of the destruction complex is critical for Wnt/β-catenin signaling. Nong et al. find that Axin undergoes liquid–liquid phase separation, which is promoted by APC. Phase-separated Axin provides a scaffold for recruitment of GSK3β, CK1α, and β-catenin and facilitates GSK3β-mediated β-catenin phosphorylation and thus degradation.
SUV39H2 epigenetic silencing controls fate conversion of epidermal stem and progenitor cells
Balmer et al. identify a new player in the complex network of epigenetic modifiers safeguarding stem and progenitor cell pools in stratified epithelia. SUV39H2, an enzyme introducing repressive methyl marks on chromatin, governs the master switch of stem and progenitor cells during epithelial fate conversion.
CENP-A overexpression promotes aneuploidy with karyotypic heterogeneity
Restricting the localization of CENP-A to centromeres is essential to prevent chromosomal instability (CIN). CENP-A is overexpressed and mislocalized in several cancers. Shrestha et al. show that overexpression of CENP-A leads to its mislocalization, CIN, and aneuploidy with karyotypic heterogeneity.
Computational analyses reveal spatial relationships between nuclear pore complexes and specific lamins
Structured illumination microscopy, cryo-ET, and computational analyses reveal that nuclear pore complexes (NPCs) and specific lamins spatially distribute in a codependent manner. Knocking out certain lamin genes or knocking down particular nucleoporins perturbs how both lamins and NPCs distribute in the nuclear envelope.
Analysis of the TORC1 interactome reveals a spatially distinct function of TORC1 in mRNP complexes
This research identifies the interactors of TORC1 by genome-wide BiFC screens and reveals that a spatially distinct portion of TORC1 interacts with RNA-binding proteins. As a component of mRNP complexes, TORC1 phosphorylates Scd6 to negatively regulate Scd6 activity in translational repression and P-body accumulation.
Superresolution characterization of core centriole architecture
Proteins within the core region of the centriole remain challenging to be resolved in vivo. Tian et al. present a spatiotemporal map of the centriole core and implications of how the proteins might interact to build the ninefold symmetrical centriole.
GTP-dependent formation of straight tubulin oligomers leads to microtubule nucleation
Ayukawa, Iwata, Imai, et al. visualize the early intermediates in the pathway of spontaneous nucleation of microtubules by using rapid flush negative stain electron microscopy. This study demonstrates that the formation of straight tubulin oligomers of critical size is essential for nucleation.
Pathogenic mutations in the kinesin-3 motor KIF1A diminish force generation and movement through allosteric mechanisms
Kinesin-3 motors are fast and superprocessive, but their force generation properties remain unclear. The authors show that KIF1A detaches under low opposing forces but rapidly reattaches to continue motility. Rapid reattachment depends on the class-specific K-loop, whereas mutations linked to neurodevelopmental disorders impair force generation and motility.
Phosphorylation of SNX27 by MAPK11/14 links cellular stress–signaling pathways with endocytic recycling
How protein endocytic recycling changes in response to environmental cues is poorly understood. Mao et al. demonstrated that multiple stresses inhibited endocytic recycling via MAPK11/14-mediated phosphorylation of SNX27 at Ser51. Phosphorylation of SNX27 decreases its binding to cargo proteins and suppresses protein endocytic recycling.
Autophagy facilitates mitochondrial rebuilding after acute heat stress via a DRP-1–dependent process
Chen et al. have studied how Caenorhabditis elegans copes with an acute heat stress that alters its development and induces the fragmentation of mitochondria. A DRP-1–dependent autophagy process takes place as part of the worm’s adaptive mechanism in response to heat stress. DRP-1 participates in the coordination between mitochondrial fission and autophagosome biogenesis.
Stochastic combinations of actin regulatory proteins are sufficient to drive filopodia formation
Dobramysl et al. find that protein complexes at filopodial tips are strongly heterogeneous. Using a combination of in vivo imaging in Drosophila, a cell-free system, and mathematical modeling, they propose that pairs of proteins form distinct subcomplexes that integrate diverse regulatory pathways to drive constrained filopodial dynamics.
Dendritic cell actin dynamics control contact duration and priming efficiency at the immunological synapse
Dendritic cell (DC) actin dynamics at the immunological synapse with T cells is partially regulated by the WAVE regulatory complex. Absence of DC WAVE leads to reduced actin dynamics, prolonged cell–cell contacts, and impaired T cell priming.
RhoGAP19D inhibits Cdc42 laterally to control epithelial cell shape and prevent invasion
Fic et al. identify Drosophila RhoGAP19D as a novel epithelial polarity factor that excludes active Cdc42 from the lateral domain. Loss of RhoGAP19D causes apical domain expansion, lateral contractility, and invasion of adjacent tissues, a phenotype resembling that of precancerous breast lesions.
A novel dual Ca2+ sensor system regulates Ca2+-dependent neurotransmitter release
Li et al. identify SNT-1 and SNT-3 as the primary and secondary Ca2+ sensors that trigger Ca2+-dependent exocytosis of synaptic vesicles at the Caenorhabditis elegans neuromuscular junction. These two Ca2+ sensors display differential domain structure and axonal distribution, and mediate synaptic vesicle release with different synaptic properties.
Completion of neuronal remodeling prompts myelination along developing motor axon branches
Postnatal motor neurons undergo extensive competitive remodeling and synchronously myelinate. Wang et al. now reveal that axon remodeling and myelination intersect. While myelination does not predetermine competition outcome, completing remodeling allows myelination to accelerate. This involves cytoskeletal maturation, which enables increased delivery of promyelinating signals.
Pluripotency state regulates cytoneme selectivity and self-organization of embryonic stem cells
Junyent et al. describe how the cell communication through cytonemes that leads to synthetic embryogenesis is altered upon pluripotency state transition in stem cells. They show that in more developmentally advanced stem cells, Wnt-iGluR crosstalk in the cytonemes is impaired, resulting in reduced formation of synthetic embryo structures.
Design of genetically encoded sensors to detect nucleosome ubiquitination in live cells
Ubiquitin conjugation to histone lysines regulates diverse processes such as gene silencing, transcriptional elongation, and DNA repair. Combining an avidity-based design strategy with molecular dynamics simulations, dos Santos Passos et al. develop genetically encoded sensors for H2AK13/15 or H2BK120 ubiquitinated nucleosomes and use them in live cells to monitor ubiquitin-dependent signaling.
Correction: Membrane expansion alleviates endoplasmic reticulum stress independently of the unfolded protein response