Issues
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Cover image
Cover Image
Cover: A circumferential rim of subplasmalemmal keratins interconnects desmosomes. The microscopic survey projection view depicts the fluorescence emitted by a keratin-8–YFP fusion in the trophectoderm of a murine blastocyst. The fusion protein is produced from a knock-in allele of the endogenous keratin 8 gene containing a YFP-encoding gene insertion at its 3'-end. Keratin filaments run parallel to the plasma membrane of adjacent cells that are connected by desmosomal cell–cell adhesions and extend toward the cell interior where they form a three-dimensional network surrounding the nucleus. Together, they form a rim and spoke network that connects the plasma membrane and nuclear compartments to support the mechanosensory functions of intermediate filaments. See article by R. A. Quinlan et al. (pp. 3437–3445).
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IN THIS ISSUE
FIRST PERSON
CELL SCIENTISTS TO WATCH
CELL SCIENCE AT A GLANCE
Actin assembly mechanisms at a glance
Summary: The morphological diversity and distinct dynamics of mammalian actin structures are established by coordinating the targeting and activation of actin filament nucleators, elongators and associated myosin motor proteins.
HYPOTHESIS
A rim-and-spoke hypothesis to explain the biomechanical roles for cytoplasmic intermediate filament networks
Summary: The cytoplasmic intermediate filament comprises a rim and spoke arrangement supporting the plasma membrane and connecting to the nucleus, to deliver their mechanosensory functions.
SHORT REPORT
Loss of OCRL increases ciliary PI(4,5)P2 in Lowe oculocerebrorenal syndrome
Summary: Lack of OCRL elevates PI(4,5)P2 levels in primary cilia of human patient cells and cells from a mouse model of Lowe syndrome, supporting a role for OCRL in ciliary phosphoinositide regulation.
RESEARCH ARTICLES
LPP3 mediates self-generation of chemotactic LPA gradients by melanoma cells
Highlighted Article: Melanoma cells can create and follow their own gradients of attractant, via a new mechanism by which tumour cells may undergo metastasis.
A PGAM5–KEAP1–Nrf2 complex is required for stress-induced mitochondrial retrograde trafficking
Summary: Mitochondria undergo retrograde trafficking in response to proteasome inhibition. Disruption of the mitochondrial PGAM5-KEAP1-Nrf2 complex leads to degradation of the mitochondrial GTPase Miro2 and inhibition of stress-induced mitochondrial trafficking.
The deubiquitylase USP10 regulates integrin β1 and β5 and fibrotic wound healing
Highlighted Article: The deubiquitylase USP10 regulates αv integrin protein levels, fibrotic markers and myofibroblast persistence in a wound. Ubiquitin-mediated pathways should thus be considered in the pathogenesis of fibrotic healing.
C-terminal motifs in promyelocytic leukemia protein isoforms critically regulate PML nuclear body formation
Summary: The formation of PML-NBs, important sub-nuclear protein structures, is differentially regulated by the unique C-terminal portion of each PML isoform.
Drosophila Atlastin in motor neurons is required for locomotion and presynaptic function
Highlighted Article: Disruption of Drosophila motor neuron Atlastin produces locomotor defects, axonal trafficking disorganization and synaptic dysfunction, providing insights into the cellular and pathological roles of neuronal atlastin in human spastic paraplegias.
Vinexin family (SORBS) proteins play different roles in stiffness-sensing and contractile force generation
Summary: Comparing the functions of vinexin family (SORBS) proteins reveals that vinexin-α and CAP regulate vinculin behavior depending on the stiffness of the extracellular matrix, while ArgBP2 plays a role in generating greater contractile forces.
Optogenetic interrogation of integrin αVβ3 function in endothelial cells
Highlighted Article: Optogenetics show that the interaction of kindlin-2 with β3 integrin and other binding partners supports endothelial cell functions relevant to angiogenesis, including sprouting and podosome formation.
LDL switches the LRP6 internalization route from flotillin dependent to clathrin dependent in hepatic cells
Summary: LRP6 is transcytosed with Niemann–Pick C1-like 1 protein, which mediates cholesterol absorption from the bile, to the apical membrane of hepatic cells, and LDL alters LRP6 trafficking to the lysosome.
Sequential activities of Dynein, Mud and Asp in centrosome–spindle coupling maintain centrosome number upon mitosis
Highlighted Article: Centrosomes are tightly coupled to the bipolar spindle. In Drosophila, Dynein and Mud initiate the centrosome–spindle coupling during prophase, whereas Asp is necessary to maintain it during metaphase.
Arl8b is required for lysosomal degradation of maternal proteins in the visceral yolk sac endoderm of mouse embryos
Summary: The small GTPase Arl8b, known to be involved in lysosomal function, contributes to mouse embryonic growth by mediating lysosomal degradation of maternal proteins in the visceral yolk sac endoderm.
Lipopolysaccharide modulates p300 and Sirt1 to promote PRMT1 stability via an SCFFbxl17-recognized acetyldegron
Summary: Bacteria-derived endotoxin LPS downregulates both the acetyltransferase p300 and the deacetylase Sirt1 to promote PRMT1 protein stability via an SCFFbxl17 E3 ligase-recognized acetydegron that augments bronchial epithelial cell overgrowth.
Association of FK506 binding proteins with RyR channels – effect of CLIC2 binding on sub-conductance opening and FKBP binding
Summary: FK506 binding proteins influence RyR gating and this contributes to excess Ca2+ release in the CLIC2 RyR channelopathy.
RETRACTION
Call for papers - Cilia and Flagella: from Basic Biology to Disease
We are welcoming submissions for our upcoming special issue: Cilia and Flagella: from Basic Biology to Disease. This issue will be coordinated by two Guest Editors: Pleasantine Mill (University of Edinburgh) and Lotte Pedersen (University of Copenhagen). Submission deadline: 1 March 2025.
Biologists @ 100 - join us in Liverpool in March 2025
We are excited to invite you to a unique scientific conference, celebrating the 100-year anniversary of The Company of Biologists, and bringing together our different communities. The conference will incorporate the Spring Meetings of the BSCB and the BSDB, the JEB Symposium Sensory Perception in a Changing World and a DMM programme on antimicrobial resistance. Find out more and register your interest to join us in March 2025 in Liverpool, UK.
Fantastic proteins and where to find them – histones, in the nucleus and beyond
In this Review, Johanna Grinat and colleagues provide an evolutionary perspective of histones, nuclear chromatin and extracellular chromatin biology, describing the known extranuclear and extracellular functions of histones.
JCS-FocalPlane Training Grants
Early-career researchers - working in an area covered by JCS - who would like to attend a microscopy training course, please apply. Deadline dates for 2025 applications: 7 March 2025 (decision by week commencing 21 April 2025) and 6 June 2025 (decision by week commencing 28 July 2025).
How to reduce your lab's carbon footprint
All stakeholders – from those working in the lab to those providing funding and infrastructure – have an important role to play to becoming more sustainable. In this Essay, Julie Welburn discusses what lab users can collectively do to transform biomedical research into a discipline that is significantly and positively sustainable.