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Vaishnavi Ananthanarayanan investigates the regulation of motor proteins and cytoskeleton–organelle interactions using single-molecule microscopy.

Spotlights

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.

Moore and Wethekam highlight work from Nsamba and colleagues that reveals that yeast α-tubulin isotypes are optimized for distinct functions.

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.

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

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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

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.

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