Issues

Byrd, Marmorale and colleagues conducted a yeast genome-wide screen to identify genes affecting TDP-43 clearance in ALS cell models. They found that ESCRT complex genes and the ubiquitin ligase Rsp5/NEDD4 facilitate TDP-43 endolysosomal clearance. TDP-43 accumulation also induces giant MVB-like organelles.

Cong et al. reveal that exportin CRM1 plays a “two birds with one stone” function by suppressing NPAT condensation and exporting NPAT to regulate histone locus body formation. Notably, instead of the “steric hindrance strategy” employed by importin, CRM1 decondensates NPAT through a “competitive occupation” model.

Arends et al. show that DUX4-induction of stable intranuclear RNA, including pericentromeric human satellite II (HSATII) repeat RNA, leads to nuclear protein aggregation. HSATII ribonucleoprotein complexes impact RNA processing downstream of DUX4 expression.

Ben-Hamo-Arad et al. reveal that Drosophila cyst cells exist in two functionally distinct subpopulations: transient escort cells derived from stem cell divisions and long-lived steady cyst cells. The latter persist at the testis apex and mediate phagoptosis, uncovering dual somatic regulation of germ cell fate.

Jacqmin et al. report that the loss of maspardin, which is deficient in spastic paraplegia 21, results in RAB7 hyperactivation due to mislocalization. This abnormal RAB7 localization leads to defects in lysosome trafficking and disruption of the mTOR–TFEB pathway.

Sebinelli, Syska, Razmazma et al. show that the yeast protein Ist2, which localizes to ER–plasma membrane contact sites, possesses phospholipid scramblase activity in its ER-localized transmembrane domain. Mutations in this domain affect ER-related processes, including COPII-mediated vesicular transport, lipid droplet homeostasis, and general phospholipid transport, demonstrating the importance of phospholipid scrambling for ER function.

An extensive ER network develops in the olfactory hair cells of Drosophila. Inagaki et al. report that the transmembrane protein Gore-tex controls a novel ER to the plasma membrane trafficking pathway essential for the cuticular nanopore formation.

Shahar et al. reveal how the malaria parasite’s apicoplast develops through four distinct stages linked to nuclear replication. They identify a unique “Crown” stage critical for organelle inheritance, establishing key connections between parasite cell cycle control, organelle genome, and apicoplast segregation.

Joly and Pintard uncover how the enzyme Katanin avoids wasting energy during microtubule remodeling. Their findings reveal how Katanin couples activation to microtubule binding, preventing futile ATP consumption and providing insights relevant to cell biology and disease.

In this work, a concerted regulatory mechanism for INF2 is described, in which INF2 is activated by a combination of calcium/calmodulin and free actin monomers. In other words, INF2 “senses” actin monomers, making monomer-binding proteins like profilin and thymosin important for INF2 regulation.

Leikina et al. propose a novel signaling pathway linking together intracellular Ca²⁺ signaling, phosphatidylserine exposure, annexin A5 binding and actin cortex detachment that facilitates osteoclast fusion and, possibly, other cell–cell fusions by promoting membrane deformations and increasing local membrane tension.

The study reveals that newly synthesized integrins can bypass the Golgi to be actively delivered to specific plasma membrane regions, where they enhance cell protrusion and adhesion. This targeted secretion rapidly increases integrin availability, giving cells dynamic flexibility to adjust to their environment.

Thomas et al. use centroid tracking to provide a live, 8-nm precision map of the actin fusion focus that underlies cell–cell fusion in Schizosaccharomyces pombe. They show that myosin V Myo52 transports the formin Fus1 along Fus1-nucleated actin filaments. This establishes positive feedback that drives actin aster formation and maintains a distal pool of secretory vesicle.

Xiong et al. present new mouse models for visualizing the selective degradation of peroxisomes (pexophagy) in living animals. The PO-TRG model reveals distinct pexophagy dynamics across tissues, during development, and in response to metabolic stress. A complementary inducible model (CA-PO-TRG) allows for cell type–specific analysis, providing sensitive tools to explore peroxisome homeostasis in health and disease.

Deng et al. summarize the physiological functions and structural basis of OSCA/TMEM63 proteins, positioning them within a mechanosensitive ion channel superfamily.

Worcester et al. describe a suite of molecular tools and approaches that can be used to probe and experimentally study lipids.

Yamasaki et al. show that GARLH proteins assemble with neuroligins to dictate synapse-type preference. Contrary to prevailing views, endogenous NL1 localizes to both excitatory and inhibitory synapses; when NL2/4 are absent or NL1-GARLH4 binding is enforced, NL1/3 assemble with GARLH4–GABA_A receptor complexes, linking neuroligins to inhibitory targeting.

Clague highlights recent work by Xiong et al. (https://doi.org/10.1083/jcb.202503169), describing a mouse model to monitor pexophagy dynamics in vivo.

Kim discusses work by Yamasaki et al. on how GARLH4 regulates neuroligin sorting, demonstrating that synapse identity is a tunable outcome of protein competition.