Podszywalow-Bartnicka and Neugebauer preview a study from the Stoecklin lab, which shows that nuclear speckles are reorganized under stress in order to facilitate efficient splicing of immediate early genes (IEGs).
Chudziak and Lee discuss findings by Desai and colleagues that resolve a long-standing mystery on how progenitor cells in the lung epithelium maintain barrier function as they respond to tissue damage.
Brown, Hell, and Gerges highlight work from Bai and colleagues that elucidates the molecular mechanisms that mediate autoinhibition and Ca2+-dependent allosteric activation of IQSEC2, which modulates synaptic plasticity and behavior.
Leisten et al. highlight recent findings regarding mitochondria–lysosome contact sites and use of super-resolution microscopy to study their contributions to cellular functions and neurological disorders.
Soliman et al. integrate recent molecular discoveries to bring insights and offer future directions to further our understanding of Topoisomerase IIA checkpoints.
Sullenberger et al. dissect the centrosomal patterning of Plk4 during centriole duplication and amplification and the positioning of Plk4 and procentrioles in relation to mother centriole microtubules. They build a molecular map of Cep57, Cep63, Cep192, and Cep152 and investigate their requirements for Plk4 localization.
Pellegrino et al. show that Mtb infection triggers an increase in the number of peroxisomes and peroxisomal ROS in human macrophages. Macrophages lacking peroxisomes are unable to restrict Mtb infection due to a decreased source of ROS, uncovering a new role for peroxisomes in the host response.
Cross et al. demonstrate that non-canonical autophagy activation, and not lysophagy, is responsible for the majority of ATG8 lipidation observed upon lysosome damage. Authors show that ATG8 proteins, directly conjugated to lysosomal membranes, engage with the lipid transfer protein ATG2.
Y. Wang et al. present a high-resolution cryo-EM structure of the mastigoneme from Chlamydomonas reinhardtii flagella. The research provides insights into the mastigoneme’s assembly mechanism and its potential roles in aiding adaptive responses to environmental changes, notably redox shifts and increased viscosity.
Using an organ-on-chip model, Boëda et al. elucidate how SCRIB controls cell and tissue shape during gut epithelium differentiation. They identify a conserved binding site for SHROOM in the SCRIB carboxy-terminal domain and show that SCRIB acts as a scaffold for SHROOM2/4 and ROCK1 to control phospho-myosin polarization.
Stress-induced nuclear speckle reorganization is linked to activation of immediate early gene splicing
Sung et al. discovered that several factors required for early steps of splicing are recruited to nuclear speckles (NSs) under conditions of ribotoxic stress. NS reorganization includes relocalization of immediate early gene (IEG) transcription foci to NSs and pronounced activation of IEG pre-mRNA splicing.
This study demonstrates that mRNA targeting and local translation at the midbody play an important role in regulating abscission during cytokinesis. It also identifies localization elements within 3′UTR on midbody-associated mRNAs as mediators of mRNA targeting the midbody.
Scott et al. show with ultrastructure expansion microscopy that self-phosphorylation is a major driver of the spatial patterning of PLK4 at the centriole and plays a critical role in selecting a single centriole duplication site.
Regulation of organelle size and integrity is essential for the proper physiological functioning of eukaryotic cells. Our research spotlights CCDC15, a novel centriole inner scaffold protein, pivotal in ensuring centriole size and integrity and regulating the formation of functional cilia.
Evidence for lung barrier regeneration by differentiation prior to binucleated and stem cell division
Lung alveoli are lined by an exquisitely thin monolayer of cells adapted for gas exchange. Guild et al. elucidate a specialized regenerative program by which this delicate, simple epithelium, continuously co-executing essential gas exchange and capillary barrier functions, is endowed with resiliency to acute injury.
Bai et al. discover that the X-linked neurodevelopmental disorder gene product IQSEC2 adopts an autoinhibited conformation that can be released by Ca2+ binding, revealing how synaptic activity is directly linked to the ISQEC2 enzymatic activity and why Iqsec2 mutations can have deleterious effect on brain functions. Their results also explain why different mutations of Iqsec2 identified in patients have different and even opposite impacts on the enzyme activity of IQSEC2.
Homeostatic mechanisms maintain the lipid compositions of organelle membranes. Acute depletion of cholesterol elicited increased synthesis of very long chain sphingolipids, which facilitate lysosome-to–plasma membrane cholesterol trafficking, plasma membrane cholesterol content, and lipid order homeostasis.
Atg15 phospholipase is activated by proteases in the yeast vacuole, allowing disruption of the inner membrane structure of autophagosomes. This study provides insights into the recycling of membrane lipids and informs work on a range of metabolic disorders.
Inhibition of lysosome-tethered Ragulator-Rag-3D complex restricts the replication of Enterovirus 71 and Coxsackie A16
Wang et al. report that the Ragulator-Rag complex recruits EV71 3D protein to the lysosomal surface, facilitating the replication of EV71 and CVA16. ZHSI-1 was identified as a novel inhibitor of EV71 and CVA16 replication, which blocks lysosomal tethering of 3D. ZHSI-1 treatment effectively protects against EV71 infection in mice.
This study applies a 3D model of a human ductal epithelium to show that Notch1 influences epithelial morphogenesis through a mechanism independent of transcriptional signaling. Notch1 cortical signaling regulates epithelial cell architecture and proliferation by directly stabilizing adherens junctions and cortical actin through the effector FAM83H.
Santos et al. show that a local energetic coupling between glycolysis and actomyosin is necessary for axonal retraction in response to repulsive cues. A complex between actomyosin and glycolytic enzymes provides the energy and mechanical force for axonal retraction.
Mature autophagosomes in the axon are transported by the microtubule motor dynein, activated by JNK-interacting proteins 3 and 4 (JIP3/4). This motility is regulated by the small GTPases ARF6 and RAB10. The tight regulation of autolysosomal transport is essential for intracellular recycling to maintain neuronal homeostasis.
Cytosolic concentrations of actin binding proteins and the implications for in vivo F-actin turnover
Gonzalez and colleagues quantify total cellular levels and free (cytosolic) concentrations of actin and 14 actin-binding proteins in budding yeast and discuss the implications of these numbers for how cells drive the rapid assembly and turnover of actin networks.
Shima et al. develop the TMEM192-mKeima probe to monitor lysophagy. They show that it detects lysophagy more specifically than the conventional Galectin3-based probes, and re-evaluate the factors involved in the lysosomal damage response. They also identify factors involved in lysophagy via screens with the probe.