Issues

Ulrichs and Shekhar highlight work from Cisterna and colleagues, which reports that microtubule number and stability increases following prolonged depletion of profilin 1 or F-actin due to a loss of actomyosin contractility.

G.W. Gant Luxton discusses new findings from the Roux group that show how changes in cellular GTP levels alter the rates of nucleocytoplasmic transport.

During ER-associated decay, unfolded membrane-resident proteins are targeted for removal and degradation by ubiquitin ligases whose identities and precise operations remain unclear. In this issue, Guerriero and Brodsky discuss new results from Kamada et al. showing the clearance of misfolded CFTR by the E3 ligase HERC3.

Stramer and Sherwood discuss recent insight into basement membrane dynamics in live animals as well as considerations for the interpretation of fluorophore-tagged BM studies.

Goldenring et al. review recent findings in cell, organoid, and animal models for monogenic diseases causing congenital diarrhea and enteropathies (CODEs).

Meng Wang and colleagues review the intricate communication between bacteria and host organelles and the impact of such communication on immune response, aging, and longevity.

Centromeric DNA regions are highly diverse and evolve rapidly. Chen et al. investigate how the correct balance of centromeric transcripts from mouse stem cells affects chromatin recruitment of CENPC and propose a model where structural RNA features, rather than sequence motifs, are key for RNA–protein interactions.

Cisterna et al. discover that microtubule number and stability increase following prolonged depletion of profilin 1 or F-actin due to the loss of actomyosin contractility. It is reversible if actomyosin is restored. This effect is more pronounced in neuronal processes and can alter organelle transport.

Baumann, Achleitner, and Tulli et al. dissect Faa1 function and recruitment during autophagy. They discover that Faa1 is directly recruited to membranes via a positive patch on the protein surface. This is a prerequisite for Faa1’s enzymatic activity sustaining autophagosome biogenesis.

Hegde et al. report that extracellular Caspase-1 functions as a chemotactic factor. This work solves the long-standing question of the cue(s) that coax the migration of HFSCs into the epidermis during the wound healing response and inflammatory skin conditions.

Wen et al. show that loss of the RNA/DNA helicase Senataxin in human cells results in aggregation of cellular proteins and proteotoxic stress. R-loop accumulation promotes an expression of non-coding RNAs from the intergenic spacer region of the ribosomal DNA, driving proteotoxic stress in the nucleolus.

Yongrong Liao et al. show how UBAP2L facilitates assembly and stability of mature NPCs at the nuclear envelope during early interphase to ensure efficient nuclear transport, adaptation to nutrient stress, and cellular proliferative capacity of human cells.

Houston et al. show that in C. elegans, BUB-1–BUB-3 kinetochore localization requires recognition of phosphorylated “TF” motifs in KNL-1 by the TPR domain of BUB-1. BUB-3 binding to phosphorylated “MELT” motifs in KNL-1 cooperates with the TPR to rapidly increase complex localization during mitotic entry.

Changes in the availability of cellular GTP resulting from physiologically relevant processes, including cell migration and cell spreading, alter the rates of Ran-dependent nuclear import and export. Altered rates of nucleocytoplasmic transport regulate RNA localization and protein synthesis.

This study demonstrates the critical role of BRG1/SMARCA4 for oligodendrocyte precursor cell differentiation and remyelination and highlights the unique dual function of BRG1/SMARCA4 in promoting oligodendrocyte differentiation and inhibiting proneuronal programs through epigenetic regulation with EED/PRC2 complexes, thereby ensuring oligodendrocyte lineage commitment and differentiation.

How the ER stress sensor IRE1α detects misfolded proteins to activate the unfolded protein response is not fully defined. Simpson et al. find that IRE1α binds a metastable structural motif in cholera toxin and other proteins that activate the UPR with implications for how binding may be linked to IRE1α activation.

RAB7A is known to recruit Rubicon, a negative regulator of autophagy, by binding to its C-terminal Rubicon Homology (RH) domain. Tudorica et al. find that RAB7A phosphorylation in PINK1/Parkin mitophagy displaces the autophagy inhibitor Rubicon, whilst recruiting the structurally related positive regulator Pacer.

Robinson et al. investigate AP-1 function using complementary approaches on cells coexpressing tagged AP-1 and cargo proteins. Their results support a model in which AP-1 is recruited onto post-Golgi carriers and early/recycling endosomes, where it retrieves selected proteins back to the TGN.

Dynamic remodeling of actin cytoskeletal networks is critical for many aspects of presynaptic plasticity. However, it remains poorly defined how presynaptic actin is regulated. Kim et al. demonstrate that the presynaptic Abl-Gef26 and Rut-cAMP-Epac pathways converge on actin-regulatory Rap1-Vav-Rac1 signaling to mediate Gbb/BMP-induced presynaptic growth and activity-induced functional plasticity, respectively.

Kamada et al. have reported that the cytosolic E3 ligase HERC3 provides a branch of the ERAD pathway for membrane proteins by recognizing the transmembrane domain.

Pinto et al. show that microglia regulate the daily plasticity of inhibitory synapses by promoting the synaptic enrichment of GABA_AR in the light/sleep phase. The molecular mechanism relies on P2RX7 signaling and microglia-derived TNFα. Microglial TNFα shapes sleep slow waves and contributes to the consolidation of memories.