Issues

Men and Hirayama et al. show that misfolded protein aggregates are degraded through microautophagy, a process mediated by the UBAP1-containing ESCRT-I complex and PTPN23. Their findings provide new insights into the mechanisms of misfolded protein aggregate clearance in cells.

Shelford, Burgess, and colleagues present a structural model of the interaction between TACC3 and ch-TOG. They discover Affimers that can inhibit this interaction and show that in cells, inhibiting the TACC3–ch-TOG interaction causes fragmentation of the mitotic pericentriolar material.

Miranda-Alban et al. uncover a synergistic interaction between the cytoplasmic tyrosine kinase Abelson and the Nedd4 family ubiquitin ligases that regulates the transit of the Notch receptor through late endosomal vesicles, thereby modulating activation of the signaling pathway in both ligand-exposed and -unexposed cells.

Mutations to the PML protein can desensitize acute promyelocytic leukemia patients to arsenic therapy. E. G Jaffray et al. characterized two common patient-derived PML mutants and revealed efficient arsenic-induced PML degradation requires both TOPORS and RNF4 SUMO-targeted ubiquitin E3 ligases and reveals SUMO paralog-preferential activities of each.

Peroxisomes are essential cellular organelles whose dysfunction leads to human diseases. Researchers identify ZBTB17 as a crucial regulator of peroxisome function through its control of protein import machinery. This discovery reveals a previously unknown regulatory mechanism of peroxisome biology and cellular metabolism.

Snx10 was found to determine the level of PI(3,5)P₂ in (phago)lysosomes by controlling the supply of PI(3)P from upstream endocytic compartments. By regulating the activity of ClC-7, a 2Cl⁻/H⁺ antiporter, PI(3,5)P₂ in turn regulates the accumulation of luminal Cl⁻ that is required for optimal hydrolase function and (phago)lysosome resolution.

Deraniyagala et al. explore the poorly understood mechanism of “intracellular counting” using the developing oral apparatus of the ciliate Tetrahymena as a model. An ortholog of importin-9 and a TPR protein MpH were found to increase and decrease the number of forming oral ciliary rows, respectively.

The study reveals that individual mitotic cyclins’ roles are more flexible than previously thought. Deficiency of B-type cyclins inhibits mitotic entry, leading to pre-NEBD mitotic slippage. Remarkably, elevating cyclin A levels can restore mitosis independently of B-type cyclins. These findings challenge traditional views on cyclin functions.

Sun et al. use cryo-electron tomography to reveal that the postsynaptic density in excitatory synapses consists of membrane-associated nanoblocks of varying sizes. These nanoblocks scaffold various postsynaptic receptor–like particles with distinct spatial organization, providing new insights into synaptic transmission and plasticity.

The transmembrane autophagy protein ATG9 is essential for autophagosome formation. Peng et al. show that scramblase-attenuated C. elegans ATG-9 mutants rescue the autophagy defect and lysosome damage caused by nondegradative autolysosomes. This uncovers the role of ATG-9 in regulating lysosome function and integrity.

In this paper, Pemberton et al. describe the generation and characterization of an engineered active fragment of the PIKfyve enzyme and its use to generate extra PI(3,5)P₂ molecules in endomembrane compartments and to test the ability of PI(3,5)P₂ sensors to detect PI(3,5)P₂ inside living cells.

Srinivasan et al. construct a collagen IV fluorophore knock-in toolkit in C. elegans using a newly identified permissive genome-editing site and reveal tissue-specific trimer diversity and basement membrane turnover defects in collagen IV mutants modeling human COL4A1/A2 (Gould) syndrome.