ON THE COVER
Nuclear divisions by mitosis in a Drosophila syncytial embryo are revealed by scanning confocal microscopy and immunofluorescence of microtubules (green), the nuclear envelope and centrosomes (red), and DNA (blue).
Image © Mehsen et al., 2018.
See page 4106.
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People & Ideas
Maria Bohnert discusses the potential functional insight into lipid droplet formation provided by Sui et al.’s new cryo-EM structure of Drosophila seipin.
McNally and Roll-Mecak review the molecular mechanism of microtubule-severing enzymes and their diverse roles in processes ranging from cell division to ciliogensis and morphogenesis.
During meiosis, unrelated chromosomes frequently become interlocked, and these structures must be removed for complete synapsis and normal chromosome segregation. Martinez-Garcia et al. show that the active removal of interlocks requires topoisomerase II and chromosome movement.
Sui et al. report the cryo-EM structure of the conserved luminal domain of the lipid droplet (LD)-formation protein seipin. The structure reveals key features of this domain and suggests a new model for seipin’s role in LD formation.
Caveolae are dynamic mechanosensors. Torrino et al. show that EHD2 plays a crucial role in the adaptation to mechanical perturbations by maintaining the caveolae reservoir at the plasma membrane after changes in membrane tension and connecting caveolae mechanosensing at the plasma membrane with the regulation of gene transcription.
Multiple proteins are dephosphorylated when mitosis finishes. Although the phosphatase PP2A-B55 promotes this process, its key substrates and functions are not clear. Mehsen et al. conducted a genetic screen in Drosophila that pointed to a role for PP2A-B55 in nuclear envelope reformation and its dephosphorylation of BAF as a crucial event.
mRNP architecture in translating and stress conditions reveals an ordered pathway of mRNP compaction
Khong and Parker use single-molecule FISH to examine the timing of mRNA entry to stress granule as well as mRNA protein complex (mRNP) architecture. mRNA compaction increases after ribosome runoff, suggesting that mRNPs preferentially adopt a closed-loop structure in nontranslating conditions.
Collins et al. use yeast genetics, biochemistry, and structure probing to dissect the role of the assembly factor Ltv1 in 40S ribosome maturation. Ribosomes from Ltv1-deficient cells have substoichiometric amounts of Rps10 and Asc1 and misfolded head rRNA, leading to defects in translational fidelity and ribosome-mediated RNA quality control, demonstrating a role for Ltv1 in chaperoning the assembly of the subunit head.
The Tau family of microtubule-associated proteins promote microtubule stabilization or regulate microtubule-based motility. Shigematsu et al. visualized MAP4 and microtubules complexed with kinesin-1 by cryo-EM, which suggests a structural basis of microtubule stabilization and kinesin inhibition by Tau family MAPs.
Shima et al. show that there is a positive cooperativity in the binding of kinesin-1 to GDP microtubules. Binding of kinesin-1 triggers conformational changes in GDP microtubules, which then take a GMPCPP-microtubule–like conformation. These effects require microtubule to bind with kinesin in the nucleotide-free state.
The GTPase atlastin mediates homotypic ER fusion through trans-crossover dimerization, but how dimerization is coupled to the GTPase cycle has remained unclear. Winsor et al. show that GTP binding causes crossover dimerization for fusion, whereas GTP hydrolysis promotes disassembly of the crossover dimer for subunit recycling.
Intracellular pathogens can modulate host Rabs and SNAREs to support their replication and immune evasion. Singh et al. show that the Salmonella effector SipA functionally mimics an R-SNARE and recruits host Q-SNAREs to promote membrane fusion. Thus, SNARE mimicry by this intracellular pathogen effector modulates the host trafficking machinery for Salmonella survival.
Differential GAP requirement for Cdc42-GTP polarization during proliferation and sexual reproduction
Local activity of the small GTPase Cdc42 is critical for cell polarization. Gallo Castro and Martin describe a new Cdc42 GTPase-activating protein (GAP) Rga3, which together with two other GAPs, constrains Cdc42-GTP zones during mitotic cycles but not during sexual reproduction.
Pulsed actomyosin contractility underlies many morphogenetic processes. Here, Michaux et al. show that, in early C. elegans embryos, pulsed contractions are generated by intrinsically excitable RhoA dynamics, involving fast autoactivation of RhoA and delayed negative feedback through local actin-dependent recruitment of the RhoGAPs RGA-3/4.
Phosphorylation of clathrin light chains (CLCs) regulates GPCR uptake but is dispensable for transferrin internalization. Maib et al. show that CLCb phosphorylation is required for efficient auxilin-mediated clathrin exchange to promote coated pit invagination in a cargo-specific manner.
Simple epithelial repair is mediated by the contraction of an actomyosin cable and cellular rearrangements at the wound edge. Carvalho et al. show that occluding junctions are required for epithelial repair by regulating these cellular rearrangements and tissue mechanical properties.
Bidirectional intraflagellar transport is restricted to two sets of microtubule doublets in the trypanosome flagellum
Intraflagellar transport (IFT) is the movement of large protein complexes responsible for the construction of cilia and flagella. Using a combination of three-dimensional electron microscopy and high-resolution live imaging, Bertiaux et al. show that IFT takes place on only four microtubule doublets out of the nine available in the trypanosome flagellum.
Louka et al. describe three conserved proteins that regulate the positions of microtubule ends near the tips of cilia. Mutations in two of these proteins cause a brain malformation, Joubert syndrome. Thus, microtubule ends in cilia may play a role in the pathology of Joubert syndrome.
Keratin 6 regulates collective keratinocyte migration by altering cell–cell and cell–matrix adhesion
Keratin 6 (K6) isoforms are induced in wound-proximal keratinocytes after injury to skin. Paradoxically, absence of K6 isoforms leads to faster directional cell migration. Wang et al. report that K6 promotes collective keratinocyte migration by interacting with desmoplakin and myosin IIA and stabilizing cell adhesion.