Issues

Sara Wickström combines biophysics, next-generation sequencing, and basic cell biology to investigate how cellular forces regulate the fate and position of stem cells within epithelial tissues.

Donker and Godinho highlight work from Ferrandiz et al. showing that ensheathing of chromosomes leads to their missegregation and promotes the formation of micronuclei.

Tait discusses optogenetic methods developed by Shkarina et al. that engage different forms of regulated cell death.

Eskandari and Eaves review evidence of caspase-3-regulated protein quality, proliferation, differentiation, and tumorigenic activity in viable cells.

Ji et al. show that the autophagy proteins VMP1 and TMEM41B are required for β-coronavirus infection, and they function at different steps during DMV biogenesis. TMEM41B is involved in nsp3/4 binding and ER zippering, while VMP1 is essential for bending the paired ER into DMVs.

Ferrandiz et al. found that misaligned chromosomes, arising from errors in mitosis, can become “ensheathed” in endomembranes. Ensheathing biases chromosomes toward missegregation, leading to aneuploidy and micronucleus formation. The authors use a novel method to remove the ensheathing membranes, which allows the spindle to rescue the chromosome.

Yang et al. unravel the molecular mechanism by which the tumor suppressor BAP1 is shuttled into the nucleus by TNPO1. TNPO1 sterically competes with UBE2O for monoubiquitination sites within the nuclear localization sequence of BAP1 to prevent its cytoplasmic retention.

Leguay et al. discovered that drugs that disassemble microtubules activate ERMs, a family of proteins that crosslink the cytoskeleton to the plasma membrane. They then found that disassembly of the microtubule array that occurs at mitotic entry is a signaling cue that promotes metaphase cell rounding via ERM activation.

Organelles are physically connected by protein bridges in membrane contact sites. Zouiouich et al. report that the MOSPD2 protein holds a second tethering activity that builds contacts between the endoplasmic reticulum and lipid droplets and contributes to the biology of lipid droplets.

Farkas et al. identify monotopic hairpin proteins as novel clients of the guided entry of tail-anchored proteins (GET) pathway. They demonstrate that high efficiency GET pathway–mediated ER targeting of the budding yeast hairpin protein Erg1, a key enzyme of sterol synthesis, becomes essential under conditions requiring increased Erg1 biogenetic flux.

Tail-anchored (TA) membrane proteins mistargeted to mitochondria are extracted by Msp1 and then transferred to the ER for further quality control. Matsumoto, Ono, et al. show that this retransfer of mistargeted TA proteins requires the operation of the GET system.

We find SHIP164 shares structural and lipid transport properties with the VPS13 family of proteins thought to transport lipids in bulk between organelles. We implicate SHIP164 in the traffic of a sub-population of endocytic vesicles, suggesting that lipid transport could play a role in their traffic.

Hooper et al. report on the role and regulation of V-ATPase in the activation of non-canonical autophagy, including LC3-associated phagocytosis. They reveal new insights into how V-ATPase V0-V1 engagement recruits the autophagy protein ATG16L1 to direct the conjugation of ATG8 to single membranes.

Chen and He find that during Drosophila mesoderm invagination mediated by apical constriction, apical actomyosin contractions induce apical transport of Rab11-marked vesicles, which in turn regulate the supracellular actomyosin network to facilitate apical constriction. These findings reveal a dynamic interplay between tissue mechanics and intracellular trafficking in morphogenesis.

Antigen cross-presenting dendritic cells (DCs) activate the ER stress sensor IRE1α without ER stress. Guttman et al. show that antigen-derived ER-imported peptides can directly engage IRE1α. Regulated IRE1α-dependent MHC-I mRNA decay curbs DC cross-presentation, while IRE1α inhibition augments antitumor immunity.

Solvik et al. reveal that the autophagy machinery facilitates the secretion of autophagy cargo receptors and other cellular components via extracellular vesicles and particles in response to lysosome inhibition or impaired autophagosome maturation.

Liu et al. reassess the cellular origin of tissue-resident macrophages in the developing heart. By generating new genetic tools, they reveal that cardiac macrophages are mainly derived from the hemogenic endothelium of yolk sac and aorta-gonad-mesonephros but not from the endocardium.

Tie et al. developed a side-averaging method to visualize the Golgi cisternal organization. They observed the progressive intra-Golgi transport of a synchronized cargo wave. Their data suggest that constitutive cargos might exit at the trans-Golgi instead of the TGN.

Shkarina et al. report the development and characterization of a new optogenetic toolset for apoptosis, necroptosis, and pyroptosis induction in humans, mice, and zebrafish. They demonstrate its application for studying the extrusion and efferocytosis of dead cells in 2D, 3D cultures, and in vivo.