Issues

Actin is vital for cell functions and is regulated by posttranslational modifications like arginylation. The structure of arginylated β-actin (R-β-actin) is nearly identical to non-modified actin. However, arginylation alters myosin-II interactions and impacts actin filament organization and cytokinesis in cells.

Wang et al. demonstrate that inward-rectifying potassium channels maintain the resting membrane potential and are required for directional sensing during neutrophil chemotaxis. It is a novel molecular mechanism by which bioelectricity regulates cell migration without affecting overall cell motility. The work is significant, given the high importance of immune cell migration in health and disease.

Nair et al. show an abundance of vesicular ERES in mammalian cells imaged by volume-focused ion beam EM. These findings reconcile diverging models of ERES architecture and establish vesicular ERES as a conserved, common feature of the early secretory pathway across diverse cell types.

Dias Maia Henriques et al. uncover an anaphase A pathway, driven by the kinesin-13 KLP-7 and opposed by the kinesin-12 KLP-18, that contributes to chromosome segregation in early C. elegans embryos. Its activity is regulated by spindle tension and cell polarity cues and progressively increases during early embryonic divisions.

A new study shows that a specific long noncoding RNA EGFR-AS1 directly facilitates the repair of broken DNA. Targeting this RNA effectively sensitizes lung cancer cells to chemotherapy, offering a promising strategy to overcome treatment resistance.

A recent model suggests the Parkinson’s risk factor protein TMEM175 is primarily a proton-conducting channel. This study demonstrates that TMEM175 does not mediate a lysosomal proton leak and is not responsible for preventing lysosomal over-acidification, providing new insights into the working mechanism of TMEM175 and its contribution to PD pathology.

ErbB3 regulates endosomal sorting and recycling of Integrin β1 in breast epithelial cells independently of ligand signaling. Its depletion redirects cargo to extracellular vesicles, impairs collective migration, and reveals a novel role of pseudo-RTKs in vesicular trafficking.

Localization of the septin cytoskeleton is controlled by regulatory factors, membrane curvature, and charge. In this study, changes to lipid composition that modulate lipid packing defects are found to impact septin assemblies in vitro and in cells.

Liu et al. discover that pathogenic bacteria use a shared strategy to exploit the host’s cellular recycling process, mitophagy. Through an effector protein that acts as an external receptor, bacteria suppress inflammatory responses to promote infection, revealing a new host–pathogen interaction mechanism.

Teng et al. investigate the cellular basis for tissue fusion during mammalian lip formation. They demonstrate that actomyosin contractility drives fusion, creating a threshold requirement for cadherin-based cell adhesion. These results also define p120-catenin molecular functions during development and implicate this mechanism in cleft lip, a common structural anomaly.

Zheng and colleagues uncover that p24/TMED family proteins mediate selective cargo translocation and release in vesicle-dependent UcPS. The switch of TMED hetero-oligomers at the ER to the UcPS cargo–stabilized homo-oligomers at the ERGIC is critical for their functions in UcPS.

Yang et al. reports that homocysteine, an intermediate in methionine-cysteine metabolism and the cause of the life-threatening disease homocystinuria, disrupts lysosomal functions by binding to and homocysteinylating V-ATPase, leading to enormous enlargement of lysosomes with extensive cargo accumulation and lysosomal membrane damage.

Li et al. show that multidomain interactions between talin and tensin3 regulate integrin activity, fibrillar adhesion formation, fibronectin assembly, and mechanosensitive tensin3 phase separation. Their findings shed light on a mechanism by which cells sense tissue mechanics and adapt adhesion signaling through the talin–tensin3 interaction.

Analysis of PIIB-type calcium pump localization and function elucidates one of the molecular mechanisms that maintains the strength of the calcium gradient during polarized growth. Quantitative examination of growth in wild type and mutants with impaired gradients provides insights into how spatial and temporal calcium signaling separately regulate cellular morphogenesis.

Budhathoki et al. show that nuclear dispersion relies on a transition from centrosomal to nucleus-associated, non-centrosomal microtubules during Drosophila tissue extension. Disrupting TIP protein function impairs ncMT stability and nuclear dispersion and reveals a fundamental antagonism between centrosomal and ncMT networks essential for epithelial remodeling.

Fazekas, Kaszás, Vámosi et al. describe a fibroblast-specific synthetic promoter, integrin α11a (itga11a)-cFos, enabling biosensor expression and targeted ablation in zebrafish fins. This tool reveals spatially distinct, sustained calcium signals in fibroblasts after tissue damage, supports characterization of the cPla2-mediated, nuclear swelling–dependent pathway, and allows investigation of fibroblast ablation and regeneration.

Cao, Peng, and Yang et al. present a high-content image-based phenotyping pipeline for quantitative analysis of organelle morphology. The interpretable feature-based method detects both prominent and subtle phenotypic changes and uncovers Golgi-cilia dynamics associated with the G0/G1 transition and AURKA activity.

Glushkova et al. develop a publicly available computational method to measure the thickness of biological membranes in cryo-electron tomograms. Analysis of algae and human cells reveals systematic membrane thickness variations within and across organelles, including thickness gradients across the Golgi apparatus that support long-standing protein sorting models.

Ivan Radin previews work from Ryken and colleagues which shows how localization and function of autoinhibitory calcium ATPases maintains the strength of the tip-focus Ca²⁺ gradient during polarized growth.

Hardin highlights recent work from Teng et al. studying the function of p120-catenin and cadherin-mediated adhesion in upper lip fusion in mammalian embryos.

Freeman and Grinstein discuss a study from Riederer et al. questioning whether TMEM175 contributes to Parkinson’s disease by serving as a pH-regulatory H⁺ channel or a K⁺ channel.