Issues
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Cover Image
Cover Image
ON THE COVER
A segmented model of cytoplasmic ribosomes associated with mitochondrial membrane in a Saccharomyces cerevisiae cell. Cytoplasmic ribosomes oriented for protein import (blue) are localized to regions where the outer-inner mitochondrial membrane distance is within 10 nm (cyan) relative to other areas of the membrane (gray). The remaining cytoplasmic ribosomes near but not oriented for protein import are shown in pink. Image © Chang et al., 2025 https://doi.org/10.1083/jcb.202407110 - PDF Icon PDF LinkTable of Contents
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In Memoriam
In Memoriam: Mike Sheetz
Wolfenson et al. recall the life and many contributions of Michael Sheetz, who passed away on January 30, 2025.
Spotlights
Lipid juggling: Any1 scrambles membranes for endosome biogenesis
Schwabl et al. discuss work from Gao et al. demonstrating that the endosomal scramblase Any1 coordinates membrane remodeling and lipid transfer via Vps13 to drive multivesicular body biogenesis.
The unexpected structure and dynamics of vimentin networks
Combining two powerful imaging techniques, Renganathan et al. provide unprecedented detail of the intermediate filament network in cells.
Reviews
Intersection of GPCR trafficking and cAMP signaling at endomembranes
Ripoll et al. review the evolving understanding of cellular GPCR signaling, highlighting recent advances and noting caveats and open questions.
Reports
Cytoplasmic ribosomes on mitochondria alter the local membrane environment for protein import
Chang et al. present a membrane-guided approach for identifying a subset of cytoplasmic ribosomes oriented for protein import on the mitochondrial surface in Saccharomyces cerevisiae using cryo-electron tomography. They show that ribosomes cluster on, make multiple contacts with, and induce local changes to the mitochondrial membrane ultrastructure at import sites.
Articles
Translation of unspliced retroviral genomic RNA in the host cell is regulated in both space and time
Leon-Diaz et al. visualize the translation of retroviral genomic RNA at the single-molecule level within cells. They discover that a minority of transcripts undergo rapid and efficient translation and that viral polysomes are located at the cell periphery, revealing spatial and temporal regulation of translation.
Centriole structural integrity defects are a crucial feature of hydrolethalus syndrome
HLS, an autosomal recessive ciliopathy, is associated with a mutation in the centriole protein HYLS1. This study shows that HYLS1 mutant mice exhibit developmental abnormalities. This mutation impairs HYLS1 localization to centrioles, which results in centriole integrity and cilia assembly defects, underlying the HLS phenotypes.
NuMA is a mitotic adaptor protein that activates dynein and connects it to microtubule minus ends
Using microscopy-based in vitro reconstitutions, Colombo et al. show that NuMA is a mitotic dynein adaptor that binds and caps microtubule minus ends, explaining how dynein, NuMA, dynactin, and Lis1 focus microtubule minus ends at mitotic spindle poles.
Arginylation of ⍺-tubulin at E77 regulates microtubule dynamics via MAP1S
MacTaggart et al. identify an ATE1-dependent arginylation site at E77 of α-tubulin and show that this modification regulates the binding of MAP1S to microtubules. Deletion of Ate1 or overexpression of non-arginylatable α-tubulin results in increased MAP1S binding and reduced microtubule dynamics.
Vimentin filament transport and organization revealed by single-particle tracking and 3D FIB-SEM
Vimentin intermediate filaments display active movement throughout the cell, with individual filaments within a bundle moving independently, as demonstrated by single-particle tracking. Three-dimensional focused ion beam scanning electron microscopy analysis revealed that vimentin intermediate filament bundles are loosely organized, occasionally aligning with microtubules at specific crossover points.
An S-acylated N-terminus and a conserved loop regulate the activity of the ABHD17 deacylase
ABHD17 enzymes remove fatty acids from membrane proteins like NRas. This study shows that their activity depends on two mobile regions: an S-acylated N-terminal helix and a loop. When these regions anchor to membranes, it correctly positions the enzyme, enabling efficient fatty acid removal from proteins.
Sphingolipid metabolism orchestrates establishment of the hair follicle stem cell compartment
This study identifies a specific role for ceramide synthase 4 (CerS4) in cell fate regulation. Epidermis-specific deletion of CerS4 prevents development of the adult hair follicle bulge stem cell compartment due to altered differentiation trajectories, resulting in hair loss and impairment in skin barrier.
RAB-10 cooperates with EHBP-1 to capture vesicular carriers during post-Golgi exocytic trafficking
This study uncovers a new mechanism for capturing lipoprotein exocytic carriers during post-Golgi trafficking. The process entails EHBP-1 in recycling endosomes capturing carriers positive for RAB-10 by interacting with active RAB-10, with LST-6 identified as the specific guanine nucleotide exchange factor (GEF) for RAB-10.
Any1 is a phospholipid scramblase involved in endosome biogenesis
This study identifies Any1 as a lipid scramblase, which cycles between Golgi and endosome and is involved in MVB biogenesis. To do so, Any1 cooperates with the lipid transfer protein Vps13, possibly at a contact site with the ER and lipid droplets.
Subversion of the host endocytic pathway by Legionella pneumophila–mediated ubiquitination of Rab5
Rab5 is a cellular GTPase essential for endocytic clearance of invading pathogens. This study reveals that the bacterial pathogen Legionella pneumophila ubiquitinates Rab5 to recruit a Rab5 inactivator RabGAP-5 to its phagosome, thereby excluding Rab5 and facilitating its intracellular replication.
The LC3-interacting region of NBR1 is a protein interaction hub enabling optimal flux
North et al. define the LC3-interacting region (LIR) of NBR1 as a multifunctional binding site that recruits ATG8 proteins, FIP200, and TAX1BP1 to drive autophagic flux. Subsequent analysis of >100 LIRs highlights these motifs as key protein interaction hotspots, shedding new light on autophagy regulation.
VPS41 recruits biosynthetic LAMP-positive vesicles through interaction with Arl8b
This study reveals a novel role of VPS41 in cellular trafficking, showing that it recruits biosynthetic LAMP carriers in a process dependent on the small GTPase Arl8b. These findings enhance our understanding of the function of VPS41 and Arl8b beyond their role in endosome–lysosome fusion.
TBC1D20 coordinates vesicle transport and actin remodeling to regulate ciliogenesis
Zhai et al. identify TBC1D20 as a novel GTPase-activating protein (GAP) for Rab11, highlighting its significant role in regulating ciliogenesis through the trafficking of ciliary vesicles and the remodeling of actin around the centrosome.
Rectification of planar orientation angle switches behavior and replenishes contractile junctions
In the early Drosophila embryo, germband extension requires positional switches of neighboring epithelial cells through remodeling of cell–cell junctions. Linvill et al. find that junctions systematically rotate from a horizontal towards a vertical orientation. During this process, rotating interfaces acquire myosin and newly initialized contractile identities, which allows for multiple rounds of intercalation.
Prickle2 regulates apical junction remodeling and tissue fluidity during vertebrate neurulation
Accurate spatial and temporal assembly and disassembly of cell–cell junctions are essential for epithelial morphogenesis. This work suggests that the core planar cell polarity protein Prickle2 cooperates with environmental cues to promote anisotropic remodeling of apical junctions, leading to neural tube closure in Xenopus embryos.
Tools
Structure of the F-tractin–F-actin complex
This study reveals the structure of F-tractin, a widely used peptide for visualizing the actin cytoskeleton, and introduces an optimized version that minimizes disruptions to actin organization. By comparing F-tractin to Lifeact, the authors highlight their similar binding modes, providing guidance for selecting actin-binding probes.
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