Issues

Wilson and colleagues use electron tomography and time-lapse fluorescence microscopy to observe that mitochondrial-derived compartments (MDCs) are generated from outer mitochondrial membrane extensions that repeatedly elongate, coalesce, and invaginate to secure membrane cargo and cytosol within a distinct, protected domain.

Wilson and colleagues observe that mitochondrial-derived compartments (MDCs) selectively incorporate proteins from only the outer mitochondrial membrane (OMM) and robustly sequester both excess and mistargeted proteins into this OMM-enriched domain, suggesting MDCs act to remove surplus hydrophobic cargo from mitochondria.

Dansu et al. identify distinct histone H4 modifications in adult oligodendrocyte progenitors compared with their neonatal counterparts. The activating H4K8ac mark regulates proliferation of adult but not neonatal oligodendrocyte progenitors, suggesting that this differentially abundant histone mark in adult progenitors modulates their functional properties.

Posttranslational modifications play a crucial role in regulating autophagy and lysosome–related transcription factor TFEB. Huang et al. find the increase in intracellular lactate induces TFEB lactylation. Lactylation at K91 protects TFEB from WWP2-mediated ubiquitination and proteasomal degradation, thereby enhancing lysosomal activity and autophagy flux.

The ER-anchored lipid transfer protein TMEM24/C2CD2L and its paralog C2CD2 mediate the formation of ER–plasma membrane junctions at sites of cell–cell contacts by interacting with band 4.1 family members and indirectly with cell adhesion proteins.

Fang et al. reveal that Kif6 and Kif9 of the kinesin-9 family play distinct roles in mammalian motile cilia. Kif6 appears to aid cargo transport along doublet microtubules to facilitate rotational polarizations of ependymal multicilia, whereas Kif9 fine-tunes ciliary beat on the central apparatus.

A crucial signaling axis involving INPP4B, PIKfyve, and TRPML-1 drives the peripheral localization of lysosomes and lysosomal exocytosis to promote migratory and invasive properties of PDAC cells. This discovery offers novel targets for therapy and a molecular explanation for the prognostic significance of INPP4B overexpression in PDAC.

Heydecker et al. use intravital subcellular microscopy to study the membrane remodeling in live mice. They show that this process requires the spatial and temporal coordination of two distinct force-generating modules composed of linear actin filaments assembled in a lattice and branched filaments organized in a network, respectively.

Ballmer et al. investigate the role of Aurora B in regulating chromosome segregation in Trypanosoma brucei, whose kinetochores consist of unique proteins. They find that Aurora B activity is required for establishing stable kinetochore–microtubule attachments and promotes mitotic exit through phosphorylation of a Bub1-like protein.

This study demonstrates that osteocytes’ expression of P2Y2 mediates actin polymerization and mitigates the anabolic response to fluid flow. In vivo studies also demonstrate that deletion of osteocytes’ P2Y2 receptor in mice enhances bone formation in response to treadmill exercise.

This study identifies Nesprin-2 as a bidirectional motor adaptor during nuclear migration in developing neurons. Nesprin-2 coordinates the dynein complex and kinesin-1 and activates prolonged bidirectional movements of the nucleus along forward-moving microtubules in migrating neurons.

Korsten et al. employ live cell imaging and expansion microscopy to show that nuclear polyQ aggregates associated with Huntington’s Disease induce nuclear envelope (NE) blebbing and cause NE ruptures. These NE ruptures often fail to repair, resulting in prolonged loss of NE integrity.

Lara-Gonzalez et al. show that cyclin B3 drives the fast pace of embryonic mitoses and is a more potent activator of Cdk1 than cyclin B1. Cyclin B1 delays anaphase by working with Cdc20 phosphorylation. Both cyclin Bs coordinate to promote fast yet accurate embryonic mitoses.

Cisneros-Soberanis et al. use electron microscopy–based 3D reconstruction of entire mitotic cells to show that chromosomes progressively condense to a remarkable near-millimolar nucleosome concentration by late prometaphase. They maintain this plateau density through early anaphase and then expand in volume just before cell division is complete.

This work develops a fast and easy-to-use protocol based on coarse-grained molecular dynamics simulations to characterize lipid binding to lipid transfer proteins (LTPs). The protocol displays accurate results on lipid binding pathways, identification of hydrophobic pockets and novel LTPs, as well as on lipid binding of multiple lipids to BLTPs.