Issues

Shi, Manzi et al. demonstrate that in polarizing epithelial spheroids from mouse embryonic stem cells, ZO-1 clusters are transported by cortical flows to establish the apical junction. Transport is driven by distinct apical and basal pools of myosin, downstream of MLCK and ROCK, respectively.

Wang et al. show that deletion of the nonhelical tailpiece (NHT) in myosin-II results in enlarged bipolar filaments with reduced bare zones, decreased disassembly, and impaired cell migration, providing mechanistic insight into disease-associated stop-codon mutations in the NHT of myosin-IIA.

Cardiomyocyte contractions require calcium transients. Liu et al. show that mitotic cardiomyocytes suppress calcium transients and remodel the sarcoplasmic reticulum/endoplasmic reticulum. These changes are required for cardiomyocyte division and identify a link between calcium signaling and cytokinesis in cardiomyocytes.

Yang et al. show that the secretory pathway kinase Fam20C is retained in the Golgi via Fam20A-mediated membrane anchoring, while the cargo receptor complex ERGIC2-ERGIC3 is critical for promoting the ER-to-Golgi transport of the Fam20A-Fam20C kinase complex. Mislocalizing Fam20C alters secretome phosphorylation, leading to reduced milk quality and subsequent growth retardation in pups.

Why F-actin is often simultaneously bundled together with multiple different bundling proteins and how these complex stable F-actin bundles undergo spatiotemporally targeted disassembly to drive cellular remodeling are poorly understood. Rajan et al. identify mechanisms for assembling and disassembling complex networks of multi-protein–bundled F-actin, including a synergism between different bundlers and disassemblers in these processes.

Hayase et al. show that E-cadherin promotes bile canaliculus elongation via RhoA activation and oriented cell division, while N-cadherin maintains hepatic polarity by attenuating RhoA, defining distinct roles of dual cadherin expression in hepatocytes.

Neurons repurpose the mitotic kinase Aurora-A for synapse formation through localized redox regulation. Gstp-mediated S-glutathionylation primes Aurora-A activation, triggering downstream signaling that drives postsynaptic maturation and revealing how spatially restricted oxidative signals achieve synaptic specificity.

Plasma membrane identity depends on tight control of anionic lipid composition, but how cells sense and correct imbalances remains poorly understood. Huang et al. find that PI4P depletion lowers phosphatidylserine and upregulates RhoB, driving phospholipase D-mediated phosphatidic acid synthesis and actin remodeling to preserve membrane structure and identity.

Begar et al. show that PCM1 multimerization nucleates centriolar satellite assembly and drives stepwise client recruitment. They further show that disrupting satellite homeostasis impairs ciliary signaling and mitotic progression. Together, these findings reveal how this membraneless organelle forms and remodels.

The discovery of a novel trafficking domain in unorthodox AQP12 yields insight into the channel’s native membrane function and its molecular regulation in intracellular yolk platelets and pancreatic zymogen granules.

Rab5-family GTPases are switched on by VPS9 GEFs and off by GAPs. Frier et al. show that the VPS9 GEF complex VINE unexpectedly recruits a phosphatase that stimulates GAP-mediated Rab5 inactivation, revealing dual control of Rab signaling by a single complex.

Muniesa-Vargas et al. use live-cell imaging to uncover how XPG activity is dynamically controlled during nucleotide excision repair. They show that TFIIH and XPA promote its recruitment, while incision by XPF and XPG, as well as the arrival of PCNA and DNA processing by EXO1, promote its release.

Winter et al. use substrate micropatterning and photoactivation to define mitochondrial subpopulations in proliferative cells. They find that biased anterograde transport from the perinuclear region asymmetrically disperses mitochondrial material. Quantitative analysis and modeling reveal that this bias sustains mitochondrial mass distribution and network connectivity.

Gaeta and Du et al. show that the epidermal stem cell layer retains its capacity for proliferation despite significant fibroblast depletion during both adult and neonatal stages in vivo. These results unmask the potential for fibroblast redundancy or compensatory activity in the dermis.

Mitochondria prioritize internal CoQ retention when mevalonate flux is compromised, creating a bioenergetic “fortress” to sustain respiration. This strategic reallocation preserves mitochondrial respiration but exhausts extramitochondrial antioxidant defenses, ultimately sensitizing the cell to ferroptotic death.

In contrast to prevailing dogma, we report that procollagen 1 assembles into a liquid condensate within cells, resolving the long-standing problem of how cells accommodate and export high concentrations of these bulky molecules from the endoplasmic reticulum.

Gao et al. identify MAI-1, a cytosolic IF1 homolog in C. elegans that rapidly translocates to severely damaged mitochondria, establishing the first genetically encoded reporter of catastrophic mitochondrial membrane damage. Using MAI-1 as a sensor, they reveal that severely damaged mitochondria are cleared through a PINK1/PARKIN-independent, LGG-1–mediated lysosomal pathway.

This study presents Met-Vision, an imaging and machine-learning approach enabling single-cell profiling of cellular energy metabolism. By revealing metabolic heterogeneity within macrophage populations, this method provides new insights into cellular metabolic states and offers a broadly applicable tool for studying metabolism across tissues at steady state and during inflammation.

Wu and Hegde annotate and analyze the topology of 4,863 human endoplasmic reticulum–inserted membrane proteins and their 20,546 transmembrane domains. Their analysis shows that transmembrane domains inserted by different pathways can tolerate different biophysical properties.

Rognoni highlights work by Gaeta, Du, and colleagues, which revealed that dermal fibroblast depletion does not affect epidermal stem cell proliferation in the skin.

José Pedro Friedmann Angeli and colleagues preview work from Ndoci et al., which reveals a system by which mitochondria prioritize CoQ retention when the mevalonate pathway is impaired, preserving respiration at the expense of antioxidant defenses.