Issues

Prinz and Hurley preview work from Li and colleagues, which uses structural analyses to reveal a new method of lipid transfer by VPS13.

Etienne-Manneville previews work from Grimsley-Myers et al., which examines the regulation of VE-cadherin endocytosis by p120catenin to modulate collective cell migration during angiogenesis.

Tan and Finkel review mitochondrial signaling pathways with a focus on unique mitochondrial lipids, innate immune signaling, and retrograde signaling.

The nuclear permeability barrier depends on closure of nuclear envelope holes. Penfield et al. show that the CNEP-1–lipin pathway limits production of ER membranes that feed into and close nuclear envelope holes. Upon excess membrane production, remodeling by nuclear envelope adaptors to ESCRT-III contributes to nuclear closure.

Structural studies by Li et al. suggest that in eukaryotes VPS13 and related proteins, like the autophagy protein ATG2, can act as bridges between organelle membranes to allow bulk lipid flow between them. Such a lipid transfer mechanism was previously known only in prokaryotes.

Mitochondria exist as a dynamic network, and their fragmentation is associated with cell death. We found that mitochondria near the cell membrane injury site rapidly fragment and enable local signaling for repair. Cells lacking this machinery fail to repair, establishing that mitochondrial fragmentation enables cell survival.

Drosophila mushroom body γ-neurons offer an excellent model to study axonal growth. Yaniv et al. show that distinct actin elongation factors are employed in different developmental and cellular contexts, providing insights into the intrinsic growth capacity of neurons, a key determinant of regeneration following injury.

A key step in accurate chromosome segregation is the removal of the outer corona of the kinetochore when microtubules are attached. Auckland et al. reveal how CENP-F stabilizes kinetochore-microtubule attachments and limits dynein-mediated corona stripping.

Mammalian oocytes need to maintain sister chromatid cohesion during their prolonged postnatal development to faithfully segregate their chromosomes in meiosis. Reichmann et al. show that Tex19.1 modulates ubiquitin-dependent proteolysis and maintains the cohesive subpopulation of cohesin in postnatal mouse oocytes to prevent oocyte aneuploidy.

The synaptonemal complex (SC) is a zipper-like protein structure that forms between paired homologous chromosomes during meiosis. Hurlock et al. discover two novel SC components, SYP-5 and SYP-6, in C. elegans and investigate their contributions in both limiting and promoting crossover formation.

Zhang et al. identify new synaptonemal complex (SC) central region proteins SYP-5 and SYP-6 in Caenorhabditis elegans and show that SC central region proteins form assembly units through stable interactions and weak interactions between the units that drive SC formation.

Au et al. delineate the autoinhibition of the microtubule- and actin-binding protein GAS2L1 and the disruption of the autoinhibition by Nek2-mediated GAS2L1 phosphorylation. They further show that the concurrent actions of Nek2 on GAS2L1 and the centrosome linker trigger centrosome disjunction for proper spindle assembly.

Yeast Psd2-catalyzed decarboxylation of phosphatidylserine to phosphatidylethanolamine is activated in a noncanonical mechanism by the Sec14-like phosphatidylinositol-transfer protein Sfh4 via a specific protein–protein interaction, and by Stt4 PtdIns 4-OH kinase–mediated control of phosphatidylserine accessibility to the enzyme.

Dynein action requires a complex of the dynein motor, the dynactin activator, and an adaptor that confers cargo specificity. The functions of different dynein adaptors are poorly understood. Spriggs et al. find that BICD adaptors can remodel a viral cargo to promote infection, revealing an unexpected function for these cellular motor adaptors in virus membrane penetration and disassembly.

Integral proteins can reach the plasma membrane via different routes. Here, Lucken-Ardjomande Häsler et al. identify three proteins that are associated with dynamic intracellular tubules, closely aligned with the ER, and involved in the transport of specific cargos whose export is particularly sensitive to ER stress.

Fascin is highly dynamic within filopodia and undergoes rapid changes in phosphorylation that dictate localized F-actin bundling activity. Pfisterer et al. show that fascin binds directly to FMNL2, and this controls fascin positioning and entry into filopodia to control filopodia stability and cell-matrix sensing.

Epithelial cell integrity and remodeling require proper actomyosin organization at adherens junctions through αE-catenin complexed with β-catenin. Sakakibara et al. show that afadin binds to αE-catenin complexed with β-catenin and enhances its F-actin–binding activity in a novel mechanism.

Grimsley-Myers et al. use mouse genetic and in vitro approaches to determine the role of the VE-cadherin-p120-catenin complex in vascular development. The results indicate that p120 stabilization of VE-cadherin is essential for vascular barrier function, whereas VE-cadherin endocytosis modulates polarized endothelial cell migration and angiogenesis.

Wang et al. find that axonal radial contractility and local expansion control the retrograde trafficking of large cargoes. The periodic actomyosin-II network comprises NM-II filaments and F-actin rings. Loss of actomyosin-II–mediated radial contractility causes defects in axonal trafficking and stability, leading to degeneration.