Issues

Gross and Graef preview two studies (Lee et al. and Tomioka et al.) describing the targeted degradation of nuclear pore complexes by selective autophagy.

Goodman previews recent work from Choudhary et al. describing how the lipid droplet assembly complex is built.

This Reproducibility Viewpoint discusses confounding factors of Tet-On/Tet-Off and Cre/loxP systems, including doxycycline-induced microbiome alterations, mitochondrial dysfunction, and tamoxifen-induced toxicity.

Five decades of ultrastructural studies of axons are reviewed and reinterpreted on the basis of current mechanistic knowledge, revealing microtubule bundles as the essential common architectural element of vertebrate and invertebrate axons.

Weavers and Martin revisit Metchnikoff’s classic observations of inflammatory cell behavior in damaged tissues and update them with the latest cell biology studies.

Cells must control the composition and location of biomolecular condensates. This study shows that phosphorylation of the RNA-binding protein Whi3 is used to regulate functionally distinct condensates important for cell polarity and nuclear division in multinucleate fungus Ashbya gossypii.

Autophagy selectively degrades a wide range of cellular components to regulate cellular functions or maintain cellular homeostasis. Tomioka et al. reveal that the nuclear pore complex and nucleoporins are degraded by selective autophagy upon inactivation of Tor kinase complex 1 in Saccharomyces cerevisiae.

OPA1 mediates inner mitochondrial fusion and mutations cause optic atrophy. Yu et al. present the crystal structure of a minimal GTPase domain of human OPA1, which sheds light on its dimerization that is physiologically important and provides an explanation for pathogenic mutations.

Gonçalves et al. show that LUZP1 is an actin-stabilizing protein localizing to the centrosome/basal body. LUZP1 and its interactor, EPLIN, restrict early steps of ciliogenesis through the modulation of actin regulators and actin at the centrosome.

Marshall-Phelps, Kegel, et al. find that disruption to the solute cotransporter NKCC1 greatly dysregulates myelin and the periaxonal space of peripheral nerves. Neurons and myelinating glia both require NKCC1 to maintain homeostasis following neuronal activity, identifying it as a critical regulator of myelinated axon physiology.

How kinesin motor proteins pick up and transport their cargo from one defined location to another is poorly understood. Serena et al. investigate how MKLP2 recognizes its cargo, the chromosome passenger complex, and promotes its transport away from chromosomes in anaphase.

Upon stress, JNK stimulates microtubule dynamics in human epithelial cell lines. Henrie et al. show that JNK phosphorylates the rescue factor CLIP-170, increasing its retention frequency on the lattice behind comets, at locations that correspond to potential future rescue sites.

Tang et al. characterize a novel proteolysis and proteasome-dependent pathway involved in degradation of unfolded antibody heavy chain (HC). Unfolded HC is ubiquitinated by N-recognin E3 ligases UBR4 and UBR5, then extracted and degraded by the proteasome. The ER luminal protease PDIA3 cleaves ubiquitinated HC to accelerate HC dislocation.

Ho et al. identified pathways, beyond lipid metabolism, that are required to maintain ER integrity and, when disrupted, activate the UPR by lipid bilayer stress through a sensor in Ire1. The resulting downstream transcriptional program differs from proteotoxic stress-induced UPR.

Combining correlative light and electron microscopy with yeast genetics and biochemistry, Gomez-Navarro, Melero, and colleagues show that cargo recruitment into a constrained COPII vesicle restricts bulk flow, thereby contributing to sorting stringency and ER quality control.

Choudhary et al. show lipid droplet (LD) biogenesis from discrete ER subdomains in yeast. Fld1 together with Nem1 localize to discrete ER subdomains independent of each other and of LDs, but both are required to recruit triacylglycerol (TAG)-synthases and LD biogenesis factors for localized TAG production and droplet assembly.

Chen et al. demonstrate that a series of developmentally orchestrated mitochondrial processes in the Drosophila early germarium, including mtDNA segregation, transcription, and replication, allow the functional manifestation of individual genomes and contribute to a selective inheritance, limiting the transmission of detrimental mtDNA mutations.

Autophagy requires the synthesis of PI(3)P and the conjugation of LC3 to the phagophore membrane. We reconstituted these two reactions and their coupling by WIPI2 and showed that positive feedback between PI3KC3-C1 and WIPI2 leads to rapid LC3 lipidation by the ATG16L1 complex.

The human ULK complex consists of ULK1/2, FIP200, ATG13, and ATG101. Shi et al. found that the FIP200 N-terminal domain is a C-shaped dimer that binds directly to a single ATG13 molecule and serves as the organizing hub of the complex.

Mammalian orthoreoviruses are nonenveloped viruses that exit cells by poorly understood nonlytic mechanisms. Fernández de Castro et al. show that modified lysosomes move toward viral replication factories and collect mature virions. Membranous carriers then emerge from these sorting organelles, transporting virions to the plasma membrane for egress.

Guadagno et al. reveal that the small GTPase Rab18, by interacting directly with the ER-resident protein kinectin, regulates the ER transport toward the cell surface to support focal adhesion growth and sustain protrusion orientation during chemotaxis.

Dong et al. discover that the pseudosubstrate region (PSr) in aPKC is a polybasic domain capable of electrostatically targeting aPKC to plasma membrane. Allosteric regulation of PSr by Par-6 couples the control of both aPKC subcellular localization and spatial activation of kinase activity.

Petzoldt et al. investigate the functional protein architecture at the presynaptic active zone, an elaborate protein scaffold organizing synaptic vesicle (SV) release. They find that the conserved multidomain protein RIM-BP provides a relay to guide SVs during their recruitment into membrane close SV release sites.

Hedgehog signaling involves the dynamic movement of receptors and effectors in and out of cilia. Desai et al. found that the dynamics of Smo are regulated by ubiquitination, which modulates its interaction with the intraflagellar transport system to control ciliary levels of this receptor.