Issues
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Cover image
Cover Image
Cover: 3D projection image of a mammary organoid isolated from Cre-ER;NMIIAfl/fl;NMIIBfl/fl;mTmG mouse treated with adenoviral Cre recombinase to generate a mixture of Cre− (red) and Cre+ (green) cells. Mosaic deletion, but not ubiquitous loss, of NMIIA and NMIIB is sufficient to induce high levels of tissue growth and cell proliferation in 3D culture and in vivo, revealing a role for NMIIA and NMIIB as negative regulators of proliferation in the mammary epithelium. See article by Nguyen-Ngoc et al. (pp. 3213–3221).
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IN THIS ISSUE
FIRST PERSON
CELL SCIENTISTS TO WATCH
OPINION
An emerging case for membrane pore formation as a common mechanism for the unconventional secretion of FGF2 and IL-1β
Summary: This Opinion article summarises the latest research into the unconventional pathways of secretion for IL-1β and FGF2.
REVIEW
Role of the ECM in notochord formation, function and disease
Summary: We review the role of ECM molecules in the formation and function of the notochord, an essential structure in all vertebrates, as well as in the pathogenesis of notochord-related diseases.
SHORT REPORT
Mosaic loss of non-muscle myosin IIA and IIB is sufficient to induce mammary epithelial proliferation
Summary: Deletion of both non-muscle myosin IIA and IIB in a mosaic subset of cells in the mammary epithelium induces tissue growth and proliferation in 3D culture and in vivo.
RESEARCH ARTICLES
Iron affects Ire1 clustering propensity and the amplitude of endoplasmic reticulum stress signaling
Highlighted Article: To respond to folding stress in the ER, cells activate the conserved sensor Ire1. We show that iron is required for optimal Ire1 activation and suggest this is because iron is required for ergosterol biosynthesis.
A genome-wide CRISPR screen reconciles the role of N-linked glycosylation in galectin-3 transport to the cell surface
Summary: A CRISPR screen identified genes that regulate the cell surface localization of galectins, and data support a secretion pathway for galectin-3 that is independent of N-linked glycoproteins and extracellular vesicles.
Sub-mitochondrial localization of the genetic-tagged mitochondrial intermembrane space-bridging components Mic19, Mic60 and Sam50
Highlighted Article: By using the novel genetic labels miniSOG and APEX2 combined with electron tomography, the sub-compartmental locations of Mic19, Mic60 and Sam50 were deciphered, which helps determine their physiological function and interaction partners.
Ca2+ coordination controls sonic hedgehog structure and its Scube2-regulated release
Summary: Different sheddases specifically and dynamically distinguish between multiple substrates expressed on the same cell, in a process regulated by Ca2+ coordination of the Shh substrate.
The serine protease inhibitor serpinB2 binds and stabilizes p21 in senescent cells
Highlighted Article: SerpinB2, a known inhibitor of urokinase plasminogen activator and tissue plasminogen activator, is a downstream target of p53 and has a role in senescence by stabilizing p21 levels.
Differential recruitment of E3 ubiquitin ligase complexes regulates RET isoform internalization
Summary: The RET receptor isoforms RET9 and RET51 recruit distinct E3 ubiquitin ligases through assembly of isoform-specific adaptor protein complexes that promote receptor ubiquitylation and internalization.
Maternal DCAF2 is crucial for maintenance of genome stability during the first cell cycle in mice
Highlighted Article: DCAF2 is a maternal factor that is crucial for prevention of DNA re-replication in the first and unique mitotic cell cycle of the zygote in mice, safeguarding zygotic genome stability.
Regulation of Cx37 channel and growth-suppressive properties by phosphorylation
Summary: Connexin 37 may serve as a molecular switch that contributes to cell fate decisions, between cell cycle arrest, cell cycle progression and cell death, in a phosphorylation- and channel-dependent manner.
Conserved cytoplasmic domains promote Hrd1 ubiquitin ligase complex formation for ER-associated degradation (ERAD)
Highlighted Article: A cytoplasmic domain within the ubiquitin ligase Hrd1 recruits cofactors necessary for ligase oligomerisation and activity, which are important for ER-associated degradation (ERAD).
The deubiquitylating enzyme Ubp12 regulates Rad23-dependent proteasomal degradation
Summary: The deubiquitylating enzyme Ubp12 targets the ubiquitin shuttle factor Rad23 and stabilizes proteasome substrates that are delivered by Rad23, uncovering a novel link between ubiquitin and proteasomal degradation.
Nup153 and Nup50 promote recruitment of 53BP1 to DNA repair foci by antagonizing BRCA1-dependent events
Summary: This study places Nup153 and Nup50 in a molecular pathway that regulates the mutual antagonism between 53BP1 and BRCA1 by promoting intranuclear targeting of 53BP1 to sites of DNA damage.
BCAP is a centriolar satellite protein and inhibitor of ciliogenesis
Summary: Cilia have important roles in cell and developmental biology but little is known about what prevents cilia being made at the wrong time. We show that BCAP is an important inhibitor of ciliogenesis.
The armadillo protein p0071 controls KIF3 motor transport
Summary: The armadillo protein p0071 controls directional vesicular transport mediated by the KIF3 (kinesin-2) complex, and secretion of respective cancer-relevant cargos from neuroendocrine and pancreatic tumor cells.
The Drosophila LC8 homolog cut up specifies the axonal transport of proteasomes
Summary: The trafficking of proteasomes, but not synaptic proteins, in Drosophila motor neurons requires the cut up gene revealing a role in cargo specificity for the LC8 family of dynein light chains.
The CCR2 3′UTR functions as a competing endogenous RNA to inhibit breast cancer metastasis
Summary: The CCR2 3′UTR acts as a metastasis suppressor by acting as a competing endogenous RNA for STARD13 and thus inhibiting activation of the RhoA–ROCK1–MLC–F-actin pathway in breast cancer cells.
PUBLISHER'S NOTES
Expression of Concern: Induction of nitric oxide synthase-2 proceeds with the concomitant downregulation of the endogenous caveolin levels. J. Cell Sci. doi: 10.1242/jcs.01002
Interviews with Biologists @ 100 conference speakers

Explore our interviews with keynote speakers from the Biologists @ 100 conference, hosted to celebrate our publisher’s 100th anniversary, where we discuss climate change and biodiversity with Hans-Otto Pörtner and Jane Francis, health and disease with Charles Swanton and Sadaf Farooqi, and emerging technologies with Manu Prakash and Jennifer Lippincott-Schwartz.
Introducing our new Associate Editors

In this Editorial, JCS Editor-in-Chief Michael Way welcomes five new Associate Editors to the JCS team. These Associate Editors will expand our support for the wider cell biology community and handle articles in immune cell biology, proteostasis, imaging and image analysis, plant cell biology, and stem cell biology and modelling.
The spatial choreography of mRNA biosynthesis

In their Review, André Ventura-Gomes and Maria Carmo-Fonseca detail the latest research progress and technological advancements that are helping to unlock how nuclear organisation underpins control of gene transcription and pre-mRNA splicing.
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: 6 June 2025 (decision by week commencing 28 July 2025) and 5 September 2025 (decision by week commencing 20 October 2025).
The emerging roles of the endoplasmic reticulum in mechanosensing and mechanotransduction

In their Review, Jonathan Townson and Cinzia Progida highlight recently emerging evidence for a role of the endoplasmic reticulum in enabling a cell to sense and respond to changes in the extracellular mechanical environment.