- Dynamics of FcγRI and SIRPα nanoclusters
Lopes et al. use superresolution microscopy to visualize the nanoscale organization of activating and inhibitory receptors on human macrophages. Nanoclusters of inhibitory SIRPα and activating FcγRI associate in the cell’s resting state, but engagement of FcγRI induces their segregation.
- Tango1 rings coordinate cargo exit from the ER
Drosophila melanogaster Tango1 is required for secretion of Collagen IV. Liu et al. use a genetic analysis to show that Tango1 is required to spatially maintain the size and integrity of ER exit site–Golgi units and that loss of Tango1 function impairs not only Collagen IV secretion but also general secretion.
- TANGO1 encircles COPII at ER exit sites
TANGO1 interacts with COPII components to generate a transport carrier for export of large cargo from the endoplasmic reticulum. Raote et al. show that TANGO1 molecules assemble to form a closed ribbon structure that encircles COPII components.
- How TPX2 promotes branching microtubule nucleation
TPX2 is required for microtubule nucleation in mitosis, but the mechanism underlying its function is unclear. Alfaro-Aco et al. analyze the domains of TPX2 necessary for its activity and identify the minimal region required for branching microtubule nucleation.
- Spectral shifts of acridine orange with CNS injury
Plemel et al. use a spectrally sensitive nucleic acid dye, acridine orange, to demonstrate a loss of RNA early during cell death. Acridine orange can also be used to distinguish apoptosis from necrosis/necroptosis in vitro and in fixed tissue samples.
- Synapse-type specific recruitment of Munc13s
Munc13 proteins are key regulators of neurotransmitter release at presynaptic active zones. Kawabe et al. describe a molecular mechanism by which the active zone protein ELKS1 recruits a functionally unique Munc13 isoform, bMunc13-2, to a defined subset of synapses.
- MPC activity regulates excitotoxicity
In cortical neurons and hippocampal slice cultures, blocking mitochondrial pyruvate uptake rewires metabolism to increase reliance on glutamate to fuel the TCA cycle. This diminishes the readily releasable pool of neuronal glutamate and minimizes the positive-feedback cascade of excitotoxic injury.
- Telomeres as therapeutic targets
Martínez and Blasco review the molecular mechanisms underlying diseases associated with telomere dysfunction, including telomeropathies, age-related disorders, and cancer. Current and future therapeutic strategies to treat and prevent these diseases, including preclinical development of telomere-targeted therapies using mouse models, are discussed.
- Membrane bending by Mic60 is conserved
The multisubunit mitochondrial contact site and cristae organizing system (MICOS) plays an important role in cristae junction formation. Tarasenko et al. show that the MICOS component Mic60 actively bends membranes and that this activity is evolutionarily conserved and necessary for cristae structure.