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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.

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.

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.

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.

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.

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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.

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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.

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