Issues

Pacheco and Hutchins preview a new study from Diaz and Mayor, which reveals the distinct force-generating mechanisms used by epithelial and mesenchymal cells during collective cell migration.

Ball and Röper discuss recent findings by Almasound et al. describing how apical–basal polarity regulates cell–cell adhesion in the Drosophila fat body.

This viewpoint presents a community-endorsed checklist defining minimal light microscopy metadata to improve rigor, reproducibility, and transparency in research.

The focal adhesion protein vinculin affects the dynamics of the actin cytoskeleton, and reorganization of the actin cytoskeleton is an energetically demanding process important in cell migration. Here, Fabiano et al. establish a relationship between vinculin, cell bioenergetics, and migration behavior, and the RhoA/ROCK/myosin II pathway in MDA-MB-231 cells.

The small GTPase Rab1 is a master regulator of Golgi traffic and autophagy. A proteomic screen identifies novel Rab1 effectors, including a dynein motor adaptor and cargo receptors for autophagy.

Bohra and Mazumder show that HP1 protein dynamics at heterochromatin damage sites differentially regulate recruitment of DSB repair factors. Disruption of phosphorylation S11–S14 residues of HP1α impairs homologous recombination. The study suggests that chromatin organization mediated by HP1 proteins influence DSB repair pathway choice.

This study demonstrates coregulation of actin filament assembly/bundling and microtubule nucleation/organization during Drosophila oogenesis, highlighting the coordinated regulation of the cytoskeleton required during development.

The type I intermediate filament keratin 15 (K15) exhibits preferential expression in a subset of skin keratinocytes with stem-like properties. We report that K15 promotes the progenitor state by counteracting the ability of the related K14 to negatively regulate YAP1, a terminal effector of Hippo signaling.

Regulation of levels of cytoskeletal building blocks is poorly understood. Using Drosophila neurons, the authors identify a pathway that communicates changes in microtubule dynamics to the nucleus. This pathway in turn modulates the expression of γTubulin, the central microtubule nucleator.

Contacts between ER and LDs not only facilitate lipid exchange but also serve as platforms for crucial subcellular processes. Viruses exploit subcellular organelles for their infection. Li et al. reveal that the NRZ tethering complex is a critical regulator of virus-induced ER–LD interactions by enhancing ER–LD contacts, thereby facilitating efficient viral infection.

Exosomes are a subpopulation of extracellular vesicles that contain a highly sorted set of protein and RNA cargos. Despite broad interest, the molecular mechanisms by which cargos are sorted into exosomes remain incomplete. In this study, Ngo et al. identify the selective autophagy receptor p62 as a quality control factor that selectively sorts cargo into exosomes.

Park et al. show that Drosophila Abi, a regulator of actin cytoskeletal dynamics, controls blood cell homeostasis by activating Notch signaling through clathrin-mediated receptor endocytosis. This regulatory process is promoted by PTP61F-mediated Abi dephosphorylation but antagonized by Abl-mediated Abi phosphorylation, revealing a reversible phosphorylation switch that integrates actin remodeling, endocytosis, and Notch signaling.

Yin et al. reveal a plasma membrane-to-lysosome signaling pathway mediated by the non-receptor tyrosine kinase FGR and the serine/threonine kinase AKT2, which regulates TFEB/TFE3 activation for lysosome biogenesis in endocytosis.

Collagen IV intercellular concentrations mediate cell–cell adhesion in the Drosophila adipose tissue. This study finds that the adipose tissue has apical-basal cell polarity, which regulates this adhesion. It further shows that during tissue remodeling, Ecdysone regulates the loss of apical-basal polarity and collagen IV intercellular concentrations to induce cell–cell dissociation and swimming migration.

Chatterjee et al. reveal that structural snapshots of different conformations of α-HL toxin from Staphylococcus aureus, such as arc-like intermediates, heptameric prepores, and pore, and octameric species, identified from the prehemolytic and posthemolytic stages, offer step-by-step oligomerization of α-HL during erythrocyte membrane lysis.

Lund et al. reveal that coupling of neuropeptide-containing dense core vesicles undergoing axonal transport to kinesin-1 and dynein is mediated by an adaptor complex composed of Syd/dJIP3/4 and RUFY, controlled by Rab2, Arl8, and the Arl8 activator BORC. Rab2-dependent sorting of membrane cargo to the vesicles is independent of the Syd–RUFY adaptor complex.

The authors show that epithelial and mesenchymal cells navigate chemical cues via fundamentally different force-generating mechanisms. Whereas epithelial groups rely on forces produced at internal junctions, mesenchymal clusters depend on coordinated supracellular contractions, offering new insight into how diverse cell types achieve collective movement during development and disease.

Collado-Diaz et al., show that lymphatic endothelial cells generate a soluble chemokine variant, CCL21-ΔC, through uPA/plasmin-dependent cleavage. This process reshapes chemokine gradients in skin and LNs, thereby regulating dendritic cell migration and positioning and uncovering a proteolytic mechanism that fine-tunes immune surveillance.

Richards et al. use live imaging of the mouse skin to visualize how melanocyte precursors (melanoblasts) migrate between adherent epithelial cells as they colonize the epidermis. They show melanoblasts form dynamic E-cadherin–based attachments to surrounding keratinocytes that are required to stabilize migratory protrusions and sustain their long-distance migration.

Jackson and Heilmann et al. use a new apical polarity reporter mouse and high-resolution live imaging to demonstrate that pancreatic tubulogenesis is driven by dynamic transformations of existing lumens, which establish and remodel the pancreatic duct. The authors also demonstrate that lumen rearrangement always precedes outer branching and provides unique niches for endocrinogenesis.

Medina, Chang et al. introduce a new method based on the Surface Morphometrics pipeline to measure global and local thicknesses of organellar membranes from cellular cryo-electron tomography data. They identified differences between organelles and membrane protein-specific changes in the cellular context.

Guo et al. introduce SynSeg, a method that eliminates manual annotation by training deep learning models on synthetic data from abstracted “primitives.” This robustly segments diverse subcellular structures, enabling high-throughput, quantitative analysis of novel, disease-related cellular phenotypes.