Issues

Ori Avinoam studies membrane remodeling with a focus on cell-to-cell fusion through the lens of correlative light and electron microscopy.

Liz Smythe highlights work from the Antonescu lab showing how clathrin coated pits segregate a subset of Akt signalling.

Patrick Caswell previews work from Duncan et al. which characterizes the mechanism by which Rab40b/Cul5 ubiquitylation of Rap2 controls its activity and correct localization during cell migration.

Bezzi previews work from Cvetkovic et al. that presents a neural organoid system to model human reactive astrocytes.

Van den Goor and Miller highlight work from the Ikenouchi lab, which shows that an interaction between tricellulin and α-catenin links tricellular junctions to the actomyosin cytoskeleton.

Mesgarzadeh et al. describe the stress-responsive signaling pathways that regulate the activity and composition of the extracellular proteostasis network.

Nedozralova et al. performed cryo-electron tomography on axon branches from mouse primary neurons and discovered concentrations of cellular activities at branching sites: ER spreading and ER comigration with microtubules, mitochondria fission, and protein synthesis in free and ER-attached polysomes.

Fan et al. quantitatively dissect the decisive regulation of migration paradigm (persistence and velocity) to the formation of the migrasome, a cellular organelle with vesicle-like morphology that mediates migracytosis. Their work adds up our current understanding of the role of cell behavior in migrasome studies.

This paper dissects the requirement for glutamine-rich prion-like domains in the formation of intranuclear CIZ1 protein assemblies at the inactive X chromosome. It highlights the influence of alternative splicing and implicates a polyglutamine domain in maintenance of the epigenetic state.

Loganathan et al. report a role for the transcriptional regulation of embryonic cell growth during Drosophila tubulogenesis. Ribbon, a BTB/POZ nuclear protein, mediates salivary gland cell growth by boosting transcription of the entire ribosomal protein gene repertoire and mediates tracheal cell growth through other targets.

Zhou et al. provide new insights to the biogenesis of mitochondrial outer membrane proteins. They demonstrate that such proteins can follow various routes where both proteinaceous elements and membrane behavior regulate the efficiency and specificity of this process.

Stormo et al. use a quantitative mass spectrometry–based approach to identify the microtubule-associated E3 ubiquitin ligase TRIM1 as a novel interacting partner of the Parkinson’s disease–driving kinase LRRK2. They find that TRIM1 recruits LRRK2 to the cytoskeleton and controls its degradation, kinase activation, and cytotoxicity.

The Rab40b/Cul5 complex is an emerging pro-migratory molecular machine. Duncan et al. demonstrate that Rab40b/Cul5 ubiquitylates Rap2 to regulate its localization and activity, ultimately proposing a model by which Rap2 is targeted to the leading-edge plasma membrane to regulate actin dynamics during cell migration.

Ono et al. revealed that mTORC2–Rab35 activation by hypo-osmotic stress not only promotes apical transport of sphingomyelin to supply membrane but also decreases the actin cortex underlining the apical membrane by reducing PI(4,5)P2 to facilitate the expansion of the apical membrane.

ANKRD24 is shown to be an additional structural protein in the stereocilia rootlet of sensory hair cells, essential for minimizing damage to rootlets. ANKRD24 binds to TRIOBP-5 and both connects TRIOBP-5 to the apical surface and organizes TRIOBP-5 within the rootlet.

Contact inhibition of locomotion is a process that regulates cell motility upon cell collision. Kummer et al. show that JAM-A inhibits the activity of the Src–Erk1/2 pathway and of Rac1 to stabilize cell matrix adhesions and to inhibit protrusive activity upon contact formation.

Ligand binding to EGF receptor (EGFR) triggers signaling and concomitant receptor recruitment to clathrin-coated pits. This study reveals that the signaling adaptor TOM1L1 recruits Fyn to a specialized subset of clathrin-coated pits and is required for SHIP2 recruitment and regulation of Akt signaling by EGFR.

Cho et al. revealed that tricellulin links tricellular junction–specific tight junction strands, the central sealing elements, with F-actin anchored end-on to tricellular junctions. This enables the converging central sealing elements to remain in proximity, which effectively closes the gap between three epithelial cells.

Varadarajan et al. find that calcium flashes regulate epithelial barrier function. Using live imaging, optogenetics, and laser-induced tight junction injury, they show that mechanosensitive channel-dependent calcium flashes promote sustained local activation of RhoA, allowing cells to repair tight junction leaks induced by mechanical stimuli.

The lysosome is the major metabolic signaling center for cells, but a detailed understanding of its biogenesis is lacking. Eising et al. combine yeast vacuole purifications and quantitative proteomics to identify cargo–receptor relationships of vacuolar proteins summarized in the yeast lysosomal biogenesis map.

Cvetkovic et al. devise a human pluripotent stem cell–based approach to rapidly generate well-defined neural organoids and to modulate activity using cell type–specific genetically encoded tools. This study also defines the dynamic reactivity of astrocytes to chronic Gq-GPCR signaling.