Issues

Cook and Hurley preview two related studies examining the role of ATG9A in autophagosome biogenesis in mammalian cells.

Hakala and Roux discuss a novel type of ESCRT-III structure found by Stempels et al. in migrating macrophages and dendritic cells, suggesting a novel, cell type-specific function for this complex.

Goranci-Buzhala and Niessen highlight work from Moore and colleagues that uses high-resolution imaging and machine learning to examine tissue-scale patterns of Ca²⁺ signaling by basal stem cells of the skin epidermis.

Kratzel and Thiel highlight work by Williams et al. revealing that ER-shaping proteins RTN3 and RTN4 are required for the formation of SARS-CoV-2 replication organelles.

Krishna and Ford discuss recent insights into how atlastins, required for homotypic fusion of ER tubules, are regulated and coordinated.

SARS-CoV-2 is the etiologic agent of COVID-19. Understanding how SARS-CoV-2 exploits host factors to replicate its genome is of great importance. Here, the authors demonstrate that two ER membrane proteins, RTN3 and RTN4, are hijacked by SARS-CoV-2 to help promote the formation of virally induced double-membrane vesicles that are critical for efficient viral genome replication.

Dabrowski et al. analyze the molecular mechanisms underlying the rapid membrane assembly of large double-membrane autophagosomes during autophagy. They discover that two conserved bridge-like tether proteins, Atg2 and Vps13, drive parallel phospholipid transfer into forming autophagosomes resulting in non-rate-limiting biogenesis.

The nuclear envelope (NE) is important for nuclear organization. This study shows that changes in NE lipid composition from treatment with a lysolipid drug decreases Sir4 association with telomeres, their clustering at the NE, and triggers lipid-specific transcriptional circuits regulated by membrane-sensing factors resulting in the formation of nuclear lipid droplets.

Moore, Bhaskar, Gao, et al. combine live imaging of the mouse epidermis and machine learning to study the role and regulation of calcium signaling within the stem cell layer. They find that cells in G2 are necessary for coordinated tissue-wide communication and reveal a feedback loop between cell cycle and calcium signaling.

Gáspár et al. reveal that sequential activity of dynein and kinesin-1 motors during transport of oskar mRNA to the posterior of the Drosophila oocyte is orchestrated by competition between two double-stranded RNA-binding proteins, Egl and Staufen, and that this process is spatio-temporally controlled by dynein-mediated localization of the staufen mRNA.

Bryce et al. show that human atlastin-3 is a robust membrane fusion catalyst that maintains ER network structure in cells. However, unlike atlastin-1/2, atlastin-3 is not C-terminally autoinhibited. This suggests that atlastin-3 is uniquely a constitutive ER fusion catalyst.

Mizuike et al. show that C10orf76, a PI4KB-binding protein, is pivotal for the ceramide transport protein CERT to act at the membrane contact sites between the endoplasmic reticulum and distal Golgi regions. This finding gives a mechanical insight into the metabolic channeling for ceramide-to-sphingomyelin conversion.

Yang et al. reveal an autoinhibitory mechanism of the centrosomin motif 1 and the relief of the autoinhibition by phosphorylation. This autoinhibition plays a role in controlling microtubule nucleation on centrosomes and the Golgi complex, and it also regulates centrosome positioning, Golgi assembly, and cell polarization.

Lawrence et al. discover that CLASPs regulate microtubule dynamics by stabilizing a metastable intermediate state of the microtubule end between growth and shrinkage. This mechanism explains CLASP-mediated microtubule regulation in essential cellular processes including cell division, migration, and differentiation.

Chen et al. identify a function of the yeast kinesin Kip2’s motor domain in recruiting free tubulin and catalyzing microtubule assembly. They provide insight into the role of the yeast CLIP-170 in microtubule elongation, that is, to act as a cofactor to track microtubule plus-ends.

Peker et al. identified a two-step import pathway allowing for dual protein localization to matrix and IMS. Weak targeting signals allow proteins to acquire stabilizing disulfide bonds in the IMS en route to the matrix. This pathway allows the sensing of import activity in two compartments.

Broadbent, Barnaba et al. analyze autophagy in living cells using HaloTagged autophagy factors to provide quantitative insight into autophagosome biogenesis, including the role of ATG2-mediated membrane tethering in the initiation of phagophores and the central role of ATG9 vesicles in autophagosome formation.

Olivas et al. demonstrate that ATG9 vesicles are the membrane seed for mammalian autophagosomes using nanodisc technology to determine co-residency of ATG9 and LC3 on autophagosomes and their precursor membranes. This work establishes a key piece of the model for autophagosome expansion via direct lipid transfer.

Rouaud et al. show that cingulin and paracingulin bind to specific myosin-2 isoforms through coiled-coil rod-mediated interactions and tether them to junctions to transmit force and modulate ZO-1 junctional accumulation, tight junction membrane tortuosity, apical membrane stiffness, and junctional architecture.

Stempels et al. discovered extremely large spiral- and ring-shaped ESCRT structures wrapping around clusters of integrins that lack actin. The micrometer-sized ESCRT structures are formed in migratory cell types and evidence suggests that they are involved in membrane repair by shedding of damaged membrane.

Chen et al. show that VAMP2 is copackaged with μ opioid receptors, but not other cargos tested, into vesicles at endosomes, and mediates the fusion of these vesicles. Such copackaging of fusion components with specific GPCRs could allow individual regulation of GPCR trafficking.

Rivero-Ríos et al. demonstrate that the SNX17-Retriever endomembrane recycling pathway at postsynaptic sites is important for synaptic function and plasticity. The authors show that NMDAR-driven CaMKII signaling recruits SNX17 and Retriever to dendritic spines in a PI3(P)-dependent manner, where it promotes long-term potentiation of synaptic efficacy.

Wong-Dilworth et al. combine CRISPR-Cas9 gene editing with STED super-resolution microscopy to reveal the specific localization of ARF GTPases on different intracellular membranes. Their nanoscale localization suggests distinct functions for ARF paralogs in intracellular trafficking.