Issues

Posor and Haucke discuss how tripartite membrane contacts between mitochondria, ER, and plasma membrane regulate mitochondrial division and PI(4)P metabolism.

Alves and Bastin highlight work from Richard Wheeler and colleagues that examines the correlation between flagellar beating patterns and intraflagellar protein trafficking.

Extracellular vesicles are known for intercellular signaling roles but can also serve to simply dispose of unwanted cargoes. In this issue, Bostelman and Broihier discuss new work from Rodal and colleagues that refutes prior work by showing that extracellular vesicles at Drosophila neuromuscular junctions are not required for signaling and instead likely serve a proteostasis role.

Néel et al. review how endolysosomes, positioned at the crossroads of multiple intracellular trafficking pathways, play critical roles in conventional and unconventional protein secretion.

Bharathan and colleagues provide a historical perspective on the discovery of the desmosome and how imaging technologies have advanced our understanding of this adhesive intercellular junction.

The anaphase spindle exhibits left-handed twist, but the source of this chirality is unknown. Neahring et al. identify two spindle motors that promote twist but find that the spindle positioning machinery counteracts it, revealing that twist is set by factors within and outside the spindle.

We used high-frame-rate, dual-color fluorescence microscopy to visualize IFT trafficking in the beating flagella of Leishmania mexicana, a uniflagellate human parasite. This revealed differing sensitivity of IFT train speed to genetically induced, mechanical, and natural changes in beating.

Maintenance of ploidy relies on Aurora-B, supported by HP1. Sako et al. report that INCENP binds to HP1 not only through the HP1-binding consensus PVI motif but also its downstream α-helical segment. This unique interface ensures a strong bond with HP1, Aurora-B activity, and mitotic fidelity.

Ugale et al. demonstrate that CDC42, ERK, and mTORC1 signaling are polarized in premitotic hematopoietic stem cells and unequally segregated during asymmetric cell division. A CDC42/ERK/mTORC1 pathway maintains HSC polarity and balances symmetric and asymmetric cell division.

Casler et al. identify that the ER-localized protein Scs2 interacts with a FFAT motif in the C-terminus of the mitochondria–PM tether Num1 to form a tripartite mitochondria–ER–PM contact site. Loss of the Num1–Scs2 interaction severely perturbs mitochondrial division rates. Unexpectedly, they also identify a novel role of mitochondria–ER–PM contact sites in regulating PM PI(4)P metabolism.

Snf1/AMPK-mediated Atg1/ULK1 activation is crucial for glucose starvation–induced autophagy. However, the activation mechanism remains poorly defined. Yao et al. demonstrate that Ca²⁺ is a critical signal linking environmental sensing to autophagy initiation by triggering Atg11–Bmh1/2–Snf1 complex assembly, which governs Atg1 activation upon glucose starvation.

Chao et al. identify a RasGAP complex that plays a specific role in the regulation of macropinosome formation. Their results demonstrate that both deletion and overexpression of this complex compromise macropinocytic activity, highlighting the importance of fine-tuning Ras activity for efficient macropinocytosis.

IQGAP1 coordinates actin assembly via transient pausing of events and by displacing prominent plus-end binding proteins including formin (mDia1), capping protein (CP), and mDia1-CP “decision complexes.”

Neurodegeneration and ciliary degeneration are caused by mutation of the deglutamylase CCP1/CCPP-1 in humans and C. elegans. The conserved NIMA-related kinase NEKL-4/NEK10 can suppress or promote degeneration in an activity-dependent manner that involves cilia–mitochondria communication and that is independent of glutamylation.

Dermal fibroblasts actively remodel pericellular type I collagen during early postnatal development. Sabeh et al. demonstrate that the membrane-anchored matrix metalloproteinase, Mmp14, serves as a requisite cell-survival factor by hydrolyzing collagen and activating β1 integrin, thereby suppressing aberrant activation of a TGF-β1/JNK-dependent apoptosis program in vivo.

This study reveals crosstalk between Sonic Hedgehog (SHH) and prostaglandin signaling pathways. SHH signaling leads to the secretion of PGE2, which activates the ciliary EP4 receptor to promote primary cilium length stability. Disruption of SHH-to-EP4 communication leads to primary cilium shortening and reduced SHH signal output.

Ball and Ghimire et al. identified that the actin-bundling protein TLNRD1 is an integral component of the CCM complex, specifically binding to CCM2. The TLNRD1–CCM2 interaction is pivotal for maintaining endothelial barrier integrity, offering new insights into CCM-related diseases.

Gera et al. identify an otherwise unappreciated physiological role of high dietary sugar–induced elevated levels of fatty acid oxidation in histone acetylation–dependent upregulation of cytokine expression. This elevated level of cytokine expression potentiates progressive cardiac fibrosis in Drosophila with far-reaching implications in diabetic fibrosis.

ESCRT depletion disrupts synaptic extracellular vesicle (EV) release without affecting signaling by several EV cargoes. EVs are phagocytosed by adjacent cells, and ESCRT disruption causes compensatory autophagy. These results suggest that EV release serves proteostatic rather than intercellular signaling functions for these cargoes at synapses.

Alvarez et al. present a Lifeact-EGFP transgenic quail that enables in vivo investigation of actin organization and dynamics during morphogenesis. Using high-resolution live imaging, they study actin structures in various contexts, demonstrating how the Lifeact-EGFP quail offers insights into tissue formation in a higher vertebrate.

Li and Gamuyao et al. engineer a synthetic lipid droplet (LD)-targeting motif and develop a tool kit that detects contact sites between LDs and other organelles. This method utilizes a reversible, split fluorescence protein (splitFAST) that enables the investigation of dynamic organelle interactions under various metabolic conditions in living cells.