Issues

In October 2023, cell biology lost one of its brightest stars, Bill Weis, gone too soon at the age of 64. Bill was a masterful biochemist and structural biologist who made landmark contributions to a remarkable number of fields, most notably cell–cell adhesion, Wnt signaling, and signaling by G-protein coupled receptors.

Gurley and Peifer highlight work from Quintanilla et al. that reveals how the local biophysical environment regulates assembly of myosin filaments.

Aristidis Moustakas discusses work from Ye-Guang Chen and colleagues on a new mechanism by which TGF-β modulates HER2 signaling in mammary epithelia.

Feringa and van der Kant discuss novel findings from the Cohen group implicating a role for the Alzheimer’s risk gene ApoE at the lipid droplet surface.

Paul Conduit previews work from Rios et al. that reveals how phosphorylation by PLK-1 induces multimerization of SPD-5 and assembly of the PCM scaffold.

Messer and Fox discuss new work that highlights the multiple molecular mechanisms by which cells respond to mitosis-related DNA damage and the danger presented by the micronucleus.

Hannaford and Rusan summarize the direct and indirect transport mechanisms by which centrosomes and centrioles are positioned in cells.

DNA combing and DNA spreading are two central approaches for studying DNA replication fork dynamics genome-wide at single-molecule resolution. Meroni et al. show that DNA combing resolves sister chromatids, allowing the detection of strand-specific alterations, whereas DNA spreading typically does not.

Suzuki et al. reveal a critical role for Vps13-mediated lipid transfer at ER–endosome contact sites in ESCRT-mediated sorting, elucidating the contribution of the ER to membrane protein sorting at endosomes.

Rios et al. investigate the structural effects of PLK-1 phosphorylation on the centrosome protein SPD-5. They reveal molecular interactions that enable maximal pericentriolar material assembly and strength in C. elegans. PLK-1 phosphorylation induces conformational changes in SPD-5, promoting multimerization via hierarchical, multivalent coiled-coil domains.

Beaumale et al report that C. elegans Katanin binding to microtubules is dictated by its p80-like (MEI-2) subunit via two microtubule-binding domains (MTBDs) and that MEI-2-mediated MT binding is essential for female meiotic spindle assembly.

The bHLH transcription factor FIT controls iron acquisition and growth in plants. FIT undergoes light-induced, reversible condensation and localizes to nuclear bodies (NBs), likely via liquid–liquid phase separation. FIT engages in protein complex, preferentially in NBs. FIT NBs are related to splicing and light signaling.

By studying a single-cell parasite, this work reveals a new contact between the energy and metabolism hub of the cell, the mitochondrion, and the organelle that hosts the cell genome, the nucleus. The contact is likely mediated by abundant and ubiquitous pores in their membranes.

Ryu et al. investigate a delivery mechanism of centriolar satellites in cilia formation. They propose that intercentriolar/rootletin fibers are used as docking sites for centriolar satellites near the centrosome based on the specific interaction of CROCC/rootletin, the main component of intercentriolar fiber, with PCM1, a scaffold of centriolar satellites.

Quintanilla et al. demonstrate that, in addition to known biochemical signaling pathways, myosin filament assembly is controlled by the local biophysical environment to enable contractile network assembly.

This study explores the impact of S477 phosphorylation on two IMPDH1 variants that play a key role in GTP synthesis in the retina. Calise et al. demonstrate that this modification increases the enzyme’s sensitivity to feedback inhibition and disrupts its assembly into high-activity filaments, serving as a mechanism to reduce retinal GTP production in the dark.

Windham et al. discover that APOE in astrocytes can traffic to lipid droplets (LDs), where it modulates LD composition and size. Astrocytes expressing the Alzheimer’s risk variant APOE4 form large LDs with impaired turnover and increased peroxidation sensitivity.

Fang et al. provide the structural and mechanistic details of how FABP7 mediates cholesterol binding and transport. They demonstrate that FABP3 and 8 can mobilize cholesterol out of lysosomes and transport the cholesterol analog in vitro, thus representing an uncharacterized group of sterol transfer proteins.

Shi et al. demonstrate that in the presence of ligand, the TGF-β type I receptor interacts with and phosphorylates HER2 at Ser779 to enhance HER2 activity, leading to AKT and ERK activation and thus promoting mammary gland development and breast cancer progression.

Rathod et al. describe the regulation of desmosomal adhesion by the mannosyl residue donor DPM1 and the protease inhibitor SERPINB5. Mechanistically, reduced desmoplakin phosphorylation resulting in enhanced plasma membrane localization is required for strong intercellular adhesion and normal epidermal differentiation.

Liang et al. develop an optogenetic tool to reconstitute focal adhesions by tuning Paxillin liquid–liquid phase separation (LLPS). They establish an essential role of Paxillin LLPS in promoting focal adhesion assembly and integrin signaling.

There is mounting evidence that the cytoskeleton organizes the plasma membrane. Due to the dynamic nature of cytoskeletal proteins, direct experimental confirmation, however, has remained elusive. This work shows in neuronal cells with a very stable cytoskeleton that periodic actin rings indeed induce membrane compartmentalization.

Scelfo et al. present an inducible, rapid, and reversible DNMT1 depletion cell system allowing DNA methylation modulation. They unveil a cooperative DNMT1 and DNMT3B activity in maintaining methylation, heterochromatin, chromatin compartmentalization, and cell fitness. Overall, this system offers temporal resolution for exploring the role of DNAme dysfunction in human disease.