Issues

Joseph Grafton Gall (1928–2024), a founder of modern cell biology, made foundational discoveries on eukaryotic chromosomes and RNA biogenesis.

Pereira and Gershlick discuss two new manuscripts revealing BEACH domain proteins’ recruitment, localization, and potential coat-like functions in trafficking.

Pons Lanau and Campelo discuss work from the De Camilli and Ji Laboratories on new roles for VPS13B in membrane trafficking and Golgi homeostasis.

Mogk and den Brave discuss exciting results from a comprehensive screen of heat shock response components in yeast, published in this issue by Pincus and colleagues. Their work reveals modulatory regulatory loops that fine-tune the timing of the shutdown of this highly conserved pathway.

Ali et al. offer a Perspective on how rather than degrading newly synthesized “orphan” proteins during stress, cells preserve them in condensates with chaperones that activate the heat shock response.

Ugur et al. characterize the bridge-like lipid transfer protein VPS13B and report its localization between Golgi cisternae and its impact on Golgi complex reformation after its BFA-induced dispersion. They also provide evidence for its functional partnership with FAM177A1, a newly identified Golgi complex protein.

In this study, West et al. define roles for Cldn7 during breast cancer invasion and metastasis. They show that Cldn7 restricts aggressive breast cancer cell behaviors by suppressing proinvasive gene expression programs, such as induction of smooth muscle actin–related genes.

de Leeuw, Budhathoki, and colleagues examine the mechanical limitations that nuclear volumes impose on epithelial remodeling in Drosophila. They identify two primary mechanisms—nuclear dispersion and nuclear deformation—that permit the resolution of internuclear tensions. Failures in both pathways lead to epithelial extrusion.

Mechanisms leading to abnormal distribution of neural progenitors during cortical development in the context of subcortical heterotopia associated with EML1 mutations remain unknown. Using a forebrain-specific mouse model and mutant human cells, this work innovatively demonstrates that by restoring microtubule function, abnormal progenitor distribution and heterotopic volume are significantly reduced.

eIF5A controls the mitochondrial protein import, and thus the mitochondrial function, by relieving ribosome stalling of mitochondrial surface-localized mRNAs encoding co-translationally imported proteins.

The mechanism by which the signal peptidase complex (SPC) distinguishes signal peptides from signal-anchored sequences remains unclear. Chung et al. demonstrate that the Spc2 subunit modulates the properties of the SPC and its surrounding membrane environment, enhancing the complex’s ability to discriminate between these sequences.

Du et al. identify Sec23IP as an adaptor that recruits VPS13B to ER exit site–Golgi interfaces, and the interaction is required for the formation of tubular ERGIC and efficient ER export of procollagen. These findings reveal a role of VPS13B–Sec23IP interaction in Cohen syndrome pathogenesis.

Domains of the ER are packaged into autophagosomes (macro-ERautophagy) during cell stress. Chidambaram et al. identify peripheral tubule junctions as a site where the autophagy receptor, RTN3L, functions. The Parkinson’s disease kinase, PINK1, regulates formation of these tubule junctions.

In this manuscript, Pankiv et al. identify BEACH domain–containing proteins (BDCPs) as novel sorting adaptors for transmembrane proteins (TMPs) in post-Golgi secretory and recycling endocytic pathways. They demonstrate that BDCPs and clathrin coat adaptors localize to distinct subdomains of secretory/recycling tubules, leading to the sorting of TMPs into distinct transport carriers.

Garde et al. comprehensively reveal how feedback regulates the heat shock response (HSR), a universally conserved gene expression program enabling cellular adaptation to stress. The HSR consists of a core feedback loop governing the expression of the chaperone Hsp70 reinforced by a stress-dependent auxiliary feedback loop controlling Hsp70 subcellular localization.

While previous work suggested that Dachsous promotes growth via the Hippo pathway and Fat represses it, Matakatsu and Fehon show that these proteins function together to restrict growth by coordinately removing a “core complex” consisting of Dachs, Dlish, and Approximated from the junctional cortex.

Zhao et al. delineate a novel mode of saturated fatty acid–induced mTORC1 activation and insulin resistance, which mediates by acetyl-CoA derived from fatty acid β oxidation and Tip60-mediated Rheb acetylation. This discovery provides therapeutic targets to intervene in the development of type 2 diabetes (T2D).

Novel in vitro assays reveal that perilipins, abundant lipid droplet proteins, differ in their sensitivity to phospholipid density of the lipid droplet monolayer, explaining how proteins distinguish between different lipid droplet populations. The work demonstrates that perilipin 3 and 4 can replace the phospholipid monolayer.

Verhoef et al. generate a Plasmodium falciparum reporter line to visualize mitochondrial dynamics in malaria parasite blood and mosquito stages. They combine high-resolution imaging methods to capture mitochondrial and apicoplast division in unprecedented detail and propose a new mechanistic model for organelle division and segregation.

Mitochondrial reactive oxygen species production is a major driver of aging and disease. Du et al. report that mitochondrial ROS production disrupts cell-cell communication by disrupting membrane receptor trafficking. Restoring endosomal trafficking of these receptors improves cell-cell signaling and rescues normal development.

Silverman et al. leveraged advanced light and electron microscopy to perform quantitative morphometry of the intestinal tuft cell cytoskeleton. Three-dimensional reconstructions of segmented image data reveal a co-aligned actin–microtubule superstructure that may play a fundamental role in tuft cell function.

The rapid swelling of yeast during hypoosmotic conditions is supported by the transport of the membrane and proteins from the ER to the cell surface. This transport seems to be mediated by the fusion of the cortical ER with the plasma membrane at membrane contact sites.

This study unveils migratory autolysosome disposal, a response to lysosomal damage where cells expel LAMP1-LC3 positive structures via autolysosome exocytosis, requiring autophagy machinery, SNARE proteins, and cell migration. This novel mechanism highlights the intricate relationship between cell migration, organelle quality control, and extracellular vesicle release.

Our study highlight an important role of CYR as a molecular brake on Rac-WRC-Arp2/3 pathway to slow down epidermal wound closure and to limit invasive collective epithelial cell migration.

Axonal regeneration is an energy-demanding process. Masin et al. show that in Pten and Socs3 co-deleted retinal ganglion cells, axonal regrowth requires and is fueled by a local axonal upregulation of glycolysis. Its targeting could provide new therapeutic avenues to induce axonal regrowth.

The newly developed ER-phagy reporter mouse models enable flexible and diverse in vivo assessments of ER-phagy and ER architecture. Significant variations in ER-phagy and the ER network are observed under physiological or pathological conditions, underscoring their broad applications in fundamental research and translational studies.