Issues
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Cover Image
Cover Image
ON THE COVER
Mitosis-specific phosphorylation of the LIC1 subunit of the cytoplasmic dynein motor is required for complete Golgi fragmentation. This confocal fluorescence micrograph of human osteosarcoma (U2OS) cells with microtubules (red), chromatin (blue), and the Golgi complex (green, GM130), shows dramatic Golgi fragmentation to a "Golgi haze" in mitosis as compared to interphase cells. Image © Kumari et al., 2021 https://doi.org/10.1083/jcb.202005184 - PDF Icon PDF LinkTable of Contents
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People & Ideas
Vaishnavi Ananthanarayanan: Advocating for women's representation in science
Vaishnavi Ananthanarayanan investigates the regulation of motor proteins and cytoskeleton–organelle interactions using single-molecule microscopy.
Spotlights
A SUMOylation wave to anchor the genome
Marston discusses work from the Wozniak laboratory showing that mitotic phosphorylation triggers a wave of SUMOylation at the nuclear envelope to re-establish chromatin tethers in late mitosis.
Specialist α-tubulins for pluralist microtubules
Moore and Wethekam highlight work from Nsamba and colleagues that reveals that yeast α-tubulin isotypes are optimized for distinct functions.
Glypicans and cytonemes unite to distribute Wnt ligands
Waghmare and Page-McCaw highlight work from Hu et al. that describes a mechanism by which convergence and extension of the mesoderm and endoderm is regulated non–cell-autonomously.
Fine-tuning activity-dependent bulk endocytosis via kinases and phosphatases
Milosevic and Cousin discuss recent work from Peng et al. showing bidirectional phosphorylation-dependent control of two discrete synaptic vesicle endocytosis modes via calcineurin and Minibrain kinase.
Articles
Persistent DNA damage signaling and DNA polymerase theta promote broken chromosome segregation
Clay et al. show that cells with DNA breaks that persist into mitosis activate sustained DNA damage signaling, regulated by Fanconi anemia proteins and the alternative end-joining repair protein DNA polymerase θ. This signaling enables broken chromosome segregation and prevents micronuclei.
Kinetochore-bound Mps1 regulates kinetochore–microtubule attachments via Ndc80 phosphorylation
Sarangapani, Koch, Nelson et al. show that phosphorylation by the conserved Mps1 kinase reduces kinetochore–microtubule attachment strength using a reconstitution system. Mps1 phosphorylates Ndc80, a microtubule-binding protein in the kinetochore, to aid mitotic error correction in cells and ensure accurate chromosome segregation.
iASPP contributes to cell cortex rigidity, mitotic cell rounding, and spindle positioning
Mangon et al. show that the protein iASPP, known as an inhibitor of p53, also interacts with the microtubule plus-end protein EB1 and the plasma membrane-to-actin cross-linker Myo1c to regulate mitotic cell cortical stiffness, mitotic rounding, and mitotic spindle positioning.
Phosphorylation-dependent mitotic SUMOylation drives nuclear envelope–chromatin interactions
Late in mitosis, chromatin interactions with the inner nuclear membrane (INM) are reestablished and passed to postmitotic nuclei. As shown in Ptak and Saik et al., in S. cerevisiae this process is supported by a wave of SUMOylation at the INM directed by the binding of the SUMO E3-ligase Siz2 to the VAP protein Scs2.
Tubulin isotypes optimize distinct spindle positioning mechanisms during yeast mitosis
Nsamba et al. use gene replacement and genome-wide screening to show the α-tubulin isotypes in budding yeast differentially recruit components of the Dynein and Kar9 pathways to microtubules and preferentially optimize these spindle positioning mechanisms. The results highlight how tubulin isotypes underlie diverse microtubule functions.
Phosphorylation and Pin1 binding to the LIC1 subunit selectively regulate mitotic dynein functions
Kumari et al. report two-tiered regulation of mitotic dynein function through the mitosis-specific, cdk1-mediated phosphorylation of its light intermediate chain 1 subunit. Either phosphorylation alone or subsequent phosphorylation-dependent recruitment of the prolyl isomerase Pin1 dictates the assembly of separate dynein-cargo adaptor complexes, which regulate distinct mitotic dynein functions.
Atg39 selectively captures inner nuclear membrane into lumenal vesicles for delivery to the autophagosome
Chandra, Mannino, Thaller et al. provide evidence for an outside–in model of nuclear autophagy that employs a resident outer nuclear membrane cargo adaptor to target the inner nuclear membrane across the nuclear envelope lumen. The inner nuclear membrane is selectively incorporated into intralumenal vesicles for delivery to the autophagosome.
Microtubule-associated proteins promote microtubule generation in the absence of γ-tubulin in human colon cancer cells
Tsuchiya and Goshima demonstrate that microtubules can be nucleated in the absence of the predominant nucleator, the γ-tubulin complex, in a human cell line both in interphase and mitosis. γ-tubulin–independent microtubule generation is promoted by the microtubule-associated proteins CLASP1 and TPX2.
Neuronal activity regulates the nuclear proteome to promote activity-dependent transcription
Herbst et al. use a novel approach for identifying activity-dependent changes in the nuclear proteome of neurons and provide evidence that regulated degradation of the tumor suppressor protein PDCD4 is required for normal activity-dependent transcription in neurons.
SORLA is required for insulin-induced expansion of the adipocyte precursor pool in visceral fat
Diet induces expansion of visceral but not subcutaneous adipose tissue from a pool of progenitor cells, contributing to the cardiometabolic risk of visceral obesity. Schmidt et al. show that the insulin-sensitizing receptor SORLA defines the unique propensity of visceral progenitors to respond to dietary signals with mitotic expansion and adipogenesis.
Tyrosine phosphorylation of S1PR1 leads to chaperone BiP-mediated import to the endoplasmic reticulum
G protein–coupled receptors (GPCRs), upon serine–threonine phosphorylation, undergo recycling or degradation. Anwar et al. demonstrate a new fate of GPCRs, exemplified by tyrosine phosphorylated sphingosine-1-phosphate receptor 1 (Y143S1PR1), which through its interaction with BiP, is routed to the endoplasmic reticulum where it dysregulates S1P-induced Ca2+ signaling and barrier function.
Programmed cortical ER collapse drives selective ER degradation and inheritance in yeast meiosis
Otto et al. show that the cortical ER undergoes programmed collapse from the plasma membrane during meiosis. Collapse separates the ER into distinct populations and determines which regions are eligible for inheritance by gametes and which are degraded by mechanisms including Atg40-mediated autophagy.
Bidirectional regulation of calcium release–activated calcium (CRAC) channel by SARAF
The molecular basis for CRAC channel regulation by the SOCE-associated regulatory factor (SARAF) remains insufficiently understood. Zomot, Achildiev et al. present a new role for SARAF in the activation of STIM1 and subsequent coupling to the Orai1 channel.
Cavin4 interacts with Bin1 to promote T-tubule formation and stability in developing skeletal muscle
Lo et al. show that Cavin4 plays a role in skeletal muscle T-tubule formation and maturation. Without Cavin4, Cav3 and caveolae accumulate in the T-tubules, which then fragment. Cavin4 is recruited by Bin1 to developing T-tubules and is required for the recycling of Cav3/caveolae back to the sarcolemma as muscle matures.
Minibrain kinase and calcineurin coordinate activity-dependent bulk endocytosis through synaptojanin
Neurons use different modes of endocytosis at synapses to maintain reliable communication across varying neural activities. This study shows that the Minibrain kinase and calcineurin switch the predominant mode of endocytosis during moderate and intense stimuli by regulating the phosphoinositol phosphatase activity of synaptojanin.
Single-particle cryo-EM reveals conformational variability of the oligomeric VCC β-barrel pore in a lipid bilayer
Sengupta et al. report the high-resolution cryo-EM structure of oligomeric VCC in a near-physiological lipid bilayer environment. Three distinct structural states indicate the conformational flexibility of the β-PFT in membranes, which may potentially guide the pore formation mechanism.
Multivalent interactions make adherens junction–cytoskeletal linkage robust during morphogenesis
Perez-Vale et al. dissect the role of the Canoe protein in adherens junction–cytoskeletal linkage, revealing that the FAB and PDZ domains play modulatory roles, while the RA domains are critical for mechanosensing and protein function. This emphasizes the role of multivalent interactions in adherens junction function.
PINK1 drives production of mtDNA-containing extracellular vesicles to promote invasiveness
Rabas et al. describe a novel means of intercellular communication in which processes evoked to mitigate cytotoxicity in metabolically stressed cells can promote PINK1-dependent packaging of mitochondrial DNA into exosomes to evoke invasive behavior in other cells.
Glypican 4 mediates Wnt transport between germ layers via signaling filopodia
Hu et al. demonstrate that transgenic expression of Glypican 4 (Gpc4) in the endoderm rescues convergence and extension (C&E) defects in all germ layers in gpc4−/− embryos. The rescue of mesoderm is mediated by Wnt5b and Wnt11f2 and depends on signaling filopodia.
Tools
High-throughput single-cell epigenomic profiling by targeted insertion of promoters (TIP-seq)
Bartlett et al. exploit linear amplification to develop an improved method (TIP-seq) to map protein binding sites in single cells, capturing 10-fold more unique reads per cell than prior methods. TIP-seq is inexpensive and scalable to thousands of cells and multiple simultaneous experiments.