People & Ideas
Ahmet Höke previews work from Li and colleagues that shows that the axonal degeneration induced by the chemotherapy agent paclitaxel is mediated by Sarm1-dependent cADPR signaling and calcium flux.
Rottner and Stradal discuss new work from the Weiner laboratory unveiling that WASP integrates substrate topology, cell polarity, and migration in immune cells.
In this review, Braschi et al. provide an updated consensus nomenclature for components of dynein motors and their assembly factors.
Golchoubian et al. show that the ER shaping protein REEP4 is a new player in nuclear pore complex (NPC) biogenesis. Their findings suggest that REEP4 cooperates with the key NPC assembly factor ELYS in late mitosis and that REEP4 may provide high-curvature ER membrane to the nascent NPC.
Opalko et al. identify the conserved GTPase Arf6 as a new regulator of fission yeast cell size. Results show that Arf6 functions as a cortical anchor for multiprotein nodes, which mediate cell size–dependent regulation of Wee1 for entry into mitosis.
San Martin et al. performed a systematic analysis of chromosome conformation across cell lines that model cancer progression, finding that rearrangement of 3D genome structure in prostate cancer is a potential mechanism for disease exacerbation and that compartment identity changes coincide with cancer progression.
Mochida et al. find that the autophagy receptor Atg39 links the outer and inner nuclear membranes via two distinct membrane-binding regions. Autophagosome formation-coupled Atg39 condensation causes local nuclear envelope protrusion, leading to sequestration of a small piece of the nucleus into the autophagosome.
Addicks et al. identify a role for protein acetylation in the regulation of muscle integrity by linking GCN5 acetyltransferase activity to the expression of dystrophin and other genes important for muscle structure. They find that this occurs through GCN5-directed acetylation of the transcriptional repressor YY1.
Keen et al. discover a new role for eIF6, a protein classically known for its role in protein synthesis, in mechanotransduction, and the cellular response to force. These data provide a novel paradigm for how the cytoskeletal and translational machineries are linked.
Human atlastin GTPases are assumed to catalyze ER membrane fusion, but their fusion activity has not previously been reconstituted. Crosby et al. show that purified atlastin1 and atlastin2 are capable of fusion catalysis and that each is negatively regulated by a variable C-terminal extension.
This study establishes that efficient delivery of progranulin and prosaposin to lysosomes is regulated at the level of exit from the ER via an interaction between prosaposin and Surf4. It thus provides new insight into ER-to-Golgi trafficking of two lysosomal proteins, with neurodegenerative disease relevance.
CRISPR screens for lipid regulators reveal a role for ER-bound SNX13 in lysosomal cholesterol export
Genome-wide CRISPR screens carried out with and without NPC1 function identify shared pathways that coordinately control lysosomal cholesterol and bis(monoacylglycero)phosphate. ER-localized SNX13 protein plays an unexpected regulatory role in modifying NPC1 function and forming membrane contacts to regulate cellular cholesterol localization.
Paramasivam et al. compared the endosomal trafficking of six LNP-mRNA formulations. LNP-mRNA accumulates in large endosomes impaired in acidification and unproductive for delivery. Super-resolution microscopy allowed visualization of single LNP-mRNA within endosomes and escape of mRNA from endosomal recycling tubules.
Aguilera et al. show that ferroptosis, an oxidative and iron-dependent form of regulated cell death, plays an important role in the cyanobacterium Synechocystis sp. PCC 6803 in response to heat stress.
Brunetti et al. demonstrate how physical and biochemical signals cooperate to pattern actin polymerization in motile neutrophils. Membrane deformations in the front half of the cell recruit WASP and elicit actin polymerization, linking substrate features with the cytoskeleton. These properties reveal a role for WASP in substrate-guided migration.
Li et al. identify cADPR as a therapeutic target for preventing paclitaxel-induced peripheral neuropathy (PIPN). The authors show that paclitaxel triggers Sarm1-dependent cADPR production, causing increased axonal calcium and degeneration. cADPR antagonists protect against PIPN in vitro and in vivo, without mitigating paclitaxel’s anti-neoplastic efficacy.
Foster et al. use cryo-electron tomography to survey the mammalian axoplasm. Highlights include determination of microtubule polarity by classification, subtomogram averaging of microtubule inner proteins (MIPs), a description of tethers linking the ER to microtubules, and the observation of numerous virus-like capsids in the axoplasm.
Uchino et al. have developed a genetically encoded probe to specifically detect the Ser2-phosphorylated, elongating form of RNA polymerase II in living cells. Ser2-phosphorylated RNA polymerase foci exhibit more dynamic motion than chromatin replication domains and p300-enriched foci.
The localized signaling mechanisms underlying how diverse synaptic connections self-assemble into functional neural circuits during mammalian brain development remain unknown. This study develops molecular tools to target signaling perturbations to defined, nascent synaptic compartments during synapse formation. These tools reveal an essential role for compartmentalized postsynaptic cAMP signaling in driving excitatory synapse assembly.