Issues

Long associated with the regulation of the endolysosomal pathway, the authors show that the PIKfyve lipid kinase extends its sphere of influence to modulate the architecture and dynamics of the ER by balancing phosphoinositide species at their inter-organellar sites.

Mori et al. demonstrate that the presynaptic active zone proteins CAST and ELKS directly interact with endophilin-A to maintain the functional synaptic vesicle pool. This study redefines their roles beyond structural organization, highlighting how they coordinate synaptic vesicle release processes necessary for efficient neurotransmission.

How SRs tether hundreds of synaptic vesicles to sustain continuous neurotransmitter release at sensory synapses remains unknown. In the current study, Gierke et al. demonstrate that the SR-associated protein Piccolino is essential for this tethering and propose a direct protein–lipid interaction as the underlying molecular mechanism.

Janssen et al. show that nanoscale membrane curvatures at asymmetric endothelial cell–cell junctions serve as a scaffold to recruit BAR proteins, including BIN1 and SNX9, during collective migration. These curvature-sensitive proteins coordinate junction remodeling, cell polarity, and directional movement, identifying membrane topology as a key organizer of endothelial guidance during vascular development.

In the Drosophila midgut, SJ proteins regulate stem cell proliferation via aPKC activity. Izumi et al. show that the exclusion of apical aPKC by SJ proteins in enteroblasts is required for stem cell homeostasis via the Kibra–Yorkie pathway.

Adhikary et al. show that PAK4 drives dynamic vertex remodeling in cells and embryos through spatiotemporal regulation of myosin II. Inhibition of PAK4 disrupts tissue packing and compromises junctional continuity and barrier function, indicating that PAK4 is essential for vertex remodeling to preserve tissue integrity.

Fan et al. reveal how nutrient sensing in intestinal epithelial cells controls stem cell activity. Inhibition of Rag GTPases or mTORC1 in enterocytes non-cell autonomously promotes ISC proliferation via Upd3–JAK–STAT signaling. In this process, Mitf activation mediates the effect of Rag GTPases but not mTORC1. These findings link dietary cues to intestinal homeostasis.

In the fruit fly, the centromeric histone CENP-A is assembled in two phases: prophase of meiosis I and postmeiosis II. Keegan et al. show that a new pool of constitutive centromere protein CENP-C is loaded at the centromere in prophase of meiosis I. This pool is critical for kinetochore assembly and meiotic chromosome segregation.

Budding yeasts are thought to use septins to mark mother–bud necks as sites for cytokinesis. Here, Colarusso et al. find that the multibudding yeast Aureobasidium pullulans can position cytokinetic machinery at most bud necks even in the absence of septins, revealing a novel pathway to mark cytokinesis sites.

Here, Sun et al. demonstrate that loss of the transcription factor STAT5A reduces α-actinin-1 expression, leading to collapse of the actin cytoskeleton. This disruption of cellular architecture alters organelle distribution, promoting mitochondrial ROS production, DNA damage, and cGAS activation, triggering innate immune responses, thus uncovering a key link between cytoskeletal integrity and innate immune regulation.

Unattached kinetochores cluster in budding yeast to promote microtubule capture. Mallett et al. dissect the molecular mechanisms of this pathway, showing Mps1 kinase regulates an interaction between Stu1 and Slk19 to drive clustering.

Liffner et al. apply MoTissU-ExM to reveal previously inaccessible details of Plasmodium sporozoite formation and salivary gland invasion. They establish a timeline for rhoptry biogenesis, distinguish rhoptry pairs, and identify RON11 as the first protein required for sporozoite rhoptry biogenesis and salivary gland epithelial cell invasion.

Saiduddin et al. use optogenetics and live imaging in Drosophila embryos to identify an unexpected role of Torso receptor tyrosine kinase in activating PI3K signaling. They demonstrate that the germplasm-specific ubiquitin ligase adaptor GCL is required to prune PIP3 from the membrane to establish the soma-germline boundary.

Branched actin networks are exposed to mechanical stress. Xiao et al. show that branch junctions whose Arp2/3 complex contains inorganic phosphate are mechanically more stable and are protected from GMF-induced destabilization, but are not stabilized further by cortactin.

The Golgi is a well-established cytoplasmic hub, yet its coordination with the nucleus remains poorly understood. Systematic analysis of Golgi–nuclear proteins uncovers a DNA repair network, where RAD51C is anchored by giantin until DNA damage triggers ATM-dependent release and nuclear import, establishing the Golgi as a spatiotemporal regulator of nuclear DNA repair.

Xue et al. reveal that during nutrient scarcity, the lipid droplet (LD)–localized PISD isoform, PISD-LD, acts as a critical metabolic switch. By bridging LDs to mitochondria for β-oxidation while simultaneously inhibiting lipophagy, PISD-LD ensures efficient cellular energy production for survival.

A scavenger receptor (CD44) and a receptor tyrosine kinase (EPHA2) join forces to mediate internalization of therapeutic ASOs into endosomes, which are then captured on the nuclear surface. Nuclear-captured endosomes become leaky, allowing ASO escape. This novel endocytic route provides insight into how ASO-mediated therapies may be optimized.

Glover et al. show that cells subject to mitochondrial protein import failure induce IMT via tunnelling nanotubes. This rescue response involves the transfer of import-defective mitochondria into healthy cells for degradation; while functional, ROS-producing mitochondria are transferred into import-compromised cells and accumulate into novel organelles (MDB) for noncanonical trans-mitophagy.