Issues

Lena Ho studies small ORF-encoded peptides (SEPs; also known as micropeptides), with a particular focus on mitochondrial SEPs, and their role in vascular biology and immunometabolism.

de Araujo and Schmidt discuss recent work from Gao et al. on differential TORC1 signaling from endosomes and the lysosomal surface.

Manzano and Martin-Belmonte previews work from Marivin et al. showing that DAPLE links junctional polarity complexes and actomyosin networks to support epithelial cell shape.

Sánchez-Álvarez and del Pozo highlight work from the Mercurio lab that shows that PD-L1 promotes front–rear polarity and migration independently of PD-1.

Hariri and Henne discuss the emerging roles for SNX-RGS proteins in interorganelle cross talk, lipid metabolism, and human diseases.

VPS13 proteins form conduits between organelles at contact sites that allow for bulk lipid flow between them. Structural studies reveal how the adaptor binding domain of VPS13 interacts with Pro-X-Pro motifs present in VPS13 receptors at organellar membranes. Importantly, supporting an emerging paradigm that proteins in this family partner with scramblases, two integral membrane proteins in the VPS13 interactome are shown to scramble glycerolipids.

Vasquez-Limeta et al. use human cells engineered for fast degradation of centrosomal protein CPAP. Using superresolution microscopy, they show that CPAP insufficiency leads to centrioles with incomplete microtubule triplets that convert to centrosomes and duplicate, but fragment owing to loss of cohesion between microtubule blades.

Using laser trapping with recombinant Ndc80 and Dam1 kinetochore complexes, Flores et al. show that interactions between three distinct regions of the complexes support strong, stable attachments to dynamic microtubule tips. Phosphorylating two of the regions reduces both attachment strength and stability. Phosphorylating the third region specifically reduces long-term stability.

Feng et al. report a meiosis-tailored mechanism of Cdc14 that governs autophagy. By dephosphorylating Atg13, Cdc14 stimulates Atg1 kinase activity and thus autophagy at anaphase I and anaphase II to facilitate meiosis progression, meiosis exit, and sporulation.

PI(4,5)P2, a key lipid at ER/PM junctions, has multiple roles in regulating TRPC channels, which includes recruitment of the channel to the junctions to facilitate activation by receptor stimulation, channel pore opening, and channel ionic selectivity.

The endosomal adaptor protein AP-3 assembles the membrane proteins of dense core vesicles (DCVs). Sorting nexin 5 targets the vesicular monoamine transporter (VMAT) to DCVs by retrograde transport from endosomes to the trans-Golgi network (TGN), thereby revealing a novel role for AP-3 at the TGN.

Through the characterization of Spiroplasma MreB5, Pande et al. show that MreB5 exhibits a nucleotide-dependent allosteric effect on filament dynamics and membrane binding. The results highlight the conserved and distinct features of MreBs in shape determination, independent of peptidoglycan synthesis machinery.

Protein condensates possess distinct material properties. Wang et al. show that the material properties of TFEB condensates govern their size and transcriptional activity. These properties can be manipulated to modulate the activity of TFEB in the autophagy-lysosome pathway.

Gao et al. show that an endosomal population carrying the TORC1 signaling complex, which they term signaling endosomes (SEs), requires the HOPS tethering complex and MVB biogenesis for their formation and identity and for efficient TORC1 signaling.

Marivin et al. show how association of the protein DAPLE with PAR polarity complexes at cell–cell junctions maintains an apical cytoskeletal network in epithelial cells by simultaneously activating heterotrimeric G proteins and recruiting the actin-stabilizing protein CD2AP.

Harmon et al. demonstrate that differential expression of an actin nucleator, the formin, Dia1, drives cell sorting and maintains distinct morphological domains within an epithelial tissue. This illuminates the possible utility of the large formin family in orchestrating the compartmentalization and differentiation of complex tissues.

Morris et al. identified a new motorized organelle, the contractomere, at the apical junction of vertebrate epithelial cells. They showed that the motility of contractomeres can alter junction proportions and the cell-packing geometry of a confluent monolayer.

Blanchette and Scalera et al. show a novel role for the endocytic machinery in regulating extracellular vesicle (EV) trafficking at Drosophila neuromuscular synapses. In endocytic mutants, EV cargoes are missorted and then removed from the synapse by retrograde transport, leading to disruption of their physiological functions.

Malin et al. show that the homophilic adhesion molecule Sidekick interacts alternately with the WAVE regulatory complex and with Polychaetoid/Zonula occludence-1 at tricellular adherens junctions to dynamically rebalance opposing protrusive and contractile forces that repeatedly expand and contract cell contacts to maintain cell–cell contacts and ensure proper epithelial remodeling.

This study reveals an unexpected cell-intrinsic function of PD-L1 in regulating the dynamics of the plasma membrane that facilitates persistent cell migration. It highlights the diverse processes that PD-L1 can regulate independently of its immune checkpoint function.