ON THE COVER
The image shows the fluorescent sterol sensor mCherry-D4H (purple) and eisosome protein Pil1-GFP (green) in ltc1Δ mutant cells treated with the Arp2/3 inhibitor CK-666. In cells lacking the Ltc1 LAM-family protein, sterols remain at the plasma membrane, which forms large invaginations co-labelled by both markers. Image © Marek et al., 2020 https://doi.org/10.1083/jcb.202001147
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Mitochondrial translation, dynamics, and lysosomes combine to extend lifespan
Ali and Haynes preview recent work from Liu et al. that provides new insight into the connection between mitochondrial dynamics, mitochondrial translation, and organismal longevity.
Microtubules keep large cells in shape
Meiring and Akhmanova preview work from Kopf et al. that shows that microtubules act to prevent cell rupture during protrusion extension in dendritic cells via regulation of actomyosin contractility.
SuperPlots: Communicating reproducibility and variability in cell biology
This Viewpoint proposes a simple way to highlight both experimental reproducibility and cell-to-cell variation, while avoiding pitfalls common in analysis of cell biology data.
Ribosome heterogeneity in stem cells and development
Li and Wang present an updated overview of ribosome heterogeneity and its functional implications in selective mRNA translational control in stem cells and development.
Autophagosome biogenesis: From membrane growth to closure
Melia et al. review the molecular mechanisms and membrane modeling events underlying autophagosome biogenesis.
Prolonged mitosis results in structurally aberrant and over-elongated centrioles
Centrioles build centrosomes and cilia, but these microtubule-based structures are frequently abnormal in tumor cells and exhibit structural aberrations such as centriole elongation. Kong et al. demonstrate that centrioles don't have an elongation monitoring mechanism, which renders them prone to over-elongation, especially during prolonged mitosis.
Factors promoting nuclear envelope assembly independent of the canonical ESCRT pathway
ESCRT makes a partial contribution to nuclear envelope fusion at the end of mitosis. Using Schizosaccharomyces japonicus, a fission yeast that undergoes mitotic NE breakdown, a forward genetic screen was performed to identify sealing mechanisms independent of the canonical ESCRT pathway.
Independent anterograde transport and retrograde cotransport of domain components of myelinated axons
The authors demonstrate anterograde vesicular transport of multiple axonal membrane proteins is largely independent, indicating that myelinated axonal domains assemble locally. In contrast, there is substantial retrograde cotransport of these proteins consistent with co-endocytosis as a clearance mechanism.
E3 ligase RFWD3 is a novel modulator of stalled fork stability in BRCA2-deficient cells
BRCA1/2 help maintain genomic integrity by stabilizing stalled forks for repair and thus act as tumor suppressors. Duan et al. identify the E3 ligase RFWD3 as a novel modulator of stalled fork stability in BRCA2-deficient cells and show that blocking fork degradation by depleting MRE11 is not sufficient for full fork recovery.
Cyclin B1-Cdk1 facilitates MAD1 release from the nuclear pore to ensure a robust spindle checkpoint
Jackman and colleagues show that Cyclin B1-Cdk1, the major mitotic kinase, binds to the spindle checkpoint protein MAD1 and synergizes with MPS1 to facilitate MAD1 release from the nuclear pore complex and recruitment to kinetochores before nuclear envelope breakdown.
Torsin ATPase deficiency leads to defects in nuclear pore biogenesis and sequestration of MLF2
Rampello et al. demonstrate that Torsin ATPases play a critical role in nuclear pore assembly and thus present mechanistic insight into DYT1 dystonia etiology. Moreover, an MLF2-based live-cell imaging platform provides temporally resolved information regarding the formation of aberrant pore structures (blebs) observed upon Torsin depletion.
MASTL promotes cell contractility and motility through kinase-independent signaling
Taskinen and Närvä et al. describe a novel kinase-independent function for MASTL in supporting cell architecture, contractility, and MRTF-A/SRF transcriptional signaling in normal breast and breast cancer cells. They reveal that MASTL-dependent regulation of these processes is important in cancer cell migration and invasion.
Phosphorylation of the microtubule-severing AAA+ enzyme Katanin regulates C. elegans embryo development
Microtubule-severing enzymes are evolutionarily conserved proteins that remodel microtubules and regulate microtubule dynamics in diverse cellular and developmental processes. Using a combination of biochemical, genetic, and live-imaging approaches, Joly et al. show how phosphorylation of the AAA+ microtubule-severing enzyme Katanin regulates its activity and stability during C. elegans development.
Mitochondrial translation and dynamics synergistically extend lifespan in C. elegans through HLH-30
Mitochondrial form and function are intimately intertwined. Liu et al. find the synergistic effect of inhibiting both mitochondrial translation and dynamics on lifespan. This synergy is dependent on the induction of lysosome biogenesis through the nuclear localization of HLH-30.
Fam20C regulates protein secretion by Cab45 phosphorylation
The TGN is a central compartment for protein sorting and secretion. Hecht et al. demonstrate that Cab45, a Ca2+-dependent sorting protein in the TGN, is phosphorylated by the Golgi kinase Fam20C. Phosphorylation of Cab45 decreases its TGN retention and increases the export of the Cab45 client LyzC.
Sterol biosensor reveals LAM-family Ltc1-dependent sterol flow to endosomes upon Arp2/3 inhibition
This work establishes the genetically encoded fluorescent sensor D4H to track sterol-rich membranes in yeast cells. Unexpectedly, disruption of the actin cytoskeleton leads to movement of sterols from the plasma membrane to endosomes. Internalization is independent of canonical vesicle trafficking and instead depends on the sterol transfer protein Ltc1.
Dscam2 suppresses synaptic strength through a PI3K-dependent endosomal pathway
Dscam2 is a cell recognition molecule involved in many aspects of neurodevelopment. Here, Odierna et al. identify a new function for this protein in regulating synaptic strength.
PD-1 and BTLA regulate T cell signaling differentially and only partially through SHP1 and SHP2
Xu et al. show that immune checkpoint receptors PD-1 and BTLA repress T cell functions through weak phosphatase SHP2 and strong phosphatase SHP1, respectively, thus avoiding competition. Surprisingly, both receptors can exert partial inhibitory effects in the absence of both SHP1 and SHP2.
Protein exchange is reduced in calcium-independent epithelial junctions
Desmosomes regulate intercellular adhesion, which controls tissue strength and plasticity. Bartle et al. show that desmosome adhesive strength is modulated through protein exchange in and out of desmosomes, not cadherin order. This exchange is tuned by desmoplakin phosphorylation, which acts as a switch between adhesive states.
Microtubules control cellular shape and coherence in amoeboid migrating cells
When cells migrate in complex environments, the dynamics of ramified protrusions need to be tightly coordinated to prevent rupture of the cell body. Kopf et al. show in dendritic cells that microtubules, via the RhoA exchange factor Lfc, prevent fragmentation by locally regulating actomyosin contractility.
KIF14 controls ciliogenesis via regulation of Aurora A and is important for Hedgehog signaling
Pejskova et al. find that KIF14 is required for cilia formation and KIF14 loss leads to Hedgehog signaling defects. The study pinpoints deregulated Aurora A activity as a downstream mediator of KIF14 deficiency and thus reveals a connection between cell cycle regulation and ciliogenesis.
Chlamydomonas PKD2 organizes mastigonemes, hair-like glycoprotein polymers on cilia
In Chlamydomonas, the TRP-channel PKD2/polycystin-2 is attached to both the axonemal microtubules and extracellular glycoprotein polymers projecting from the ciliary surface. The design suggests a mechanosensory role of PKD2 in motile cilia.
CRISPR-Cas12a–assisted PCR tagging of mammalian genes
Fueller et al. describe a simple one-step procedure for quick and scalable chromosomal tagging of genes in mammalian cells using PCR products that contain all elements necessary for Cas12a tagging: homology arms and a guide RNA gene for chromosomal insertion, the tag (such as GFP), and a selection marker.
TRPA1-dependent calcium transients and CGRP release in DRG neurons require extracellular calcium
Refutation of TRPA1-mediated lysosomal calcium release in sensory neurons, emphasizing the requirement and influx of extracellular calcium through TRPA1 for activation.
Reply to “TRPA1-dependent calcium transients and CGRP release in DRG neurons require extracellular calcium”
TRPA1 is a nonselective cation channel implicated in thermosensation and inflammatory pain. Liu et al. validated that TRPA1 activation not only triggers Ca2+ influx through the plasma membrane, but also elicits Ca2+ release from endolysosomes, which directly triggers vesicle exocytosis and contributes to nocifensive sensation.