Collectively our data indicate that Homers link cell polarity cues to the coordination of YAP and Wnt pathway activity. In addition, Homer condensates are tunable signaling hubs that might be deregulated in response to polarity loss and thereby contribute to YAP/Wnt hyper-activation in cancers
We further find that Homers phase separate in the cytoplasm and that PatJ and FRYL differentially modulate the material properties and signaling outputs of these condensates. PatJ in particular has a striking effect on Homer phase separation in response to osmotic stress
Whilst FRYL and PatJ antagonise Homers pro-YAP function, they both cooperate with Homers in promoting Wnt pathway activity. Taken together, we propose that Homers suppress FRYL/NDR to promote YAP activation, whilst polarity cues transmitted via PatJ suppress Homers to shut down the pathway
Some highlights: We find that Homers promote YAP and Wnt pathway activity in several polarised and non-polarised cells. They interact with the Crumbs complex protein PatJ and the NDR kinase scaffold FRYL. These interactions are mediated via PxxF motifs in PatJ/FRYL and the Homer EVH1 domain.
Good news from the ALab. We have just resubmitted our revised manuscript on the role of Homer proteins in YAP-Wnt signaling crosstalk. Here's the updated preprint: doi.org/10.1101/2025.... We’re truly grateful to the reviewers for their thoughtful comments and questions and hope they'll be happy...
James, J., Winn, L. B., Mottram-Epson, P., & Köster, D. (2025). Paths to stability–actin regulation of adherens junction mechanics. Journal of Cell Science, #EpitheilalMechanicsReview doi.org/10.1242/jcs....
Would like to be added here - thank you!
An Archaea bacterium with an internal membrane system! Amazing and beautiful work!
Congrats Sandra!
1/11 In @science.org: A new perspective on how our intestines renew. Cells are not “pushed out” by crowding or die from apoptosis. Instead, cells play a mechanical tug-of-war, where weaker cells extrude, reframing gut renewal as force-regulated. www.science.org/doi/10.1126/...
Supracellular actomyosin assemblies: master coordinators of development
In this Review, Katja Röper @katjaroeper.bsky.social discusses supracellular actomyosin structures, tissues where they function, their known roles as well as potential properties
journals.biologists.com/dev/article/...
Our latest efforts to understand Enterococcal wound infection. In long-term collaboration with @gthibault.bsky.social, we discovered how E. faecalis makes extracellular ROS - via EET!⚡️Which in turn dysregulates host UPR to delay wound healing. Led by @aarontan.bsky.social - his videos below are 🤩!
We have some news! We find that the post-synaptic Homer proteins coordinate YAP and Wnt signaling in epithelial cells, downstream of the Crumbs polarity complex. They do so by sequestering YAP and beta-catenin in biomolecular condensates, and by suppressing a FRYL/NDR complex. Check it out!
Announcing a new @embo.org Workshop on "Intracellular mechanics and organelle mechanobiology" that we are organizing with Michael Krieg and Verena Ruprecht at @icfo.eu (Barcelona) on 16-20 February, 2026. Please, repost and spread the word! 🙏 #EMBOmechanobio
meetings.embo.org/event/26-org...
EMBO Cell Polarity and Membrane Dynamics workshop is off to a good start - as always :) #EMBO
A) Diagram of the RUSH system. The Halo-tagged cargo is retained in the ER by the binding of the Streptavidin binding peptide (SBP) to Streptavidin (StrepA), which is fused to the ER retention signal, KDEL. The cargo is synchronously released upon the addition of biotin, which outcompetes SBP for binding to Streptavidin.B) Diagram of the tagged cargo constructs used in this study. C) Steady state expression of UAS-SBP-Halo-Cadherin99c (magenta) under the control of traffic jam-Gal4, showing its localization to the apical microvilli. Phalloidin staining of F-actin (green) labels the apical microvilli in the follicle cells and the oocyte. Scale bar 10 µm. D) Steady state expression of UAS-SBP-SNAP-Ndg (magenta) under the control of traffic jam-Gal4, showing its localization to the basement membrane. Actin is shown in green. Scale bar 10 µm. E) En face view of SBP-SNAP-Ndg in the basement membrane. Scale bar 10 µm. F) Time course of SBP-Halo-Cadherin99C trafficking in fixed samples. G) 25 min after release from the ER, Cad99c (green) localizes to subapical puncta that are labeled by Rab11 (magenta). Scale bar 10 µm. In all figures with a cross-section of the follicle cells, apical is toward the top of the image and basal toward the bottom.
How are specific cargos targeted to apical & basolateral domains within #EpithelialCells? This study uses a novel #vesicle tracking software "MSP-tracker" to show that the secretory pathway in #Drosophila follicle cells is unexpectedly spatially organized @plosbiology.org 🧪 plos.io/3EfJsBp
Entzugserscheinungsangst :)
Our paper on the regulation of the tight junction leak pathway by Arhgap12/N-Wasp is out ! www.cell.com/cell-reports...
Why am I not surprised…
Altogether we propose that the fusion of VACs with the AMIS provides an efficient mechanism for the rapid specification of apical domain identity. In addition, Pals1 and PatJ appear to be critical for VAC fusion at the AMIS, possibly due to their role in regulating the apical actin cytoskeleton.
Finally, we asked how VAC exocytosis at the AMIS is regulated and found that loss of the Crb complex proteins Pals1 or PatJ results in the intracellular accumulation of VACs and severe defects in lumen formation. Apical actin levels and the apical cell cortex were markedly altered in PatJ KO cells.
We further present evidence that VACs arise from the internalisation of microvilli-enriched membrane pits at the ECM facing side of cell doublets. How these membrane pits are internalised and how VACs are trafficked to and fuse with the AMIS is currently unclear.
We then analysed lumen initiation in MDCK 3D cultures. Using LM and EM we identified intracellular VACs and observed fusion events of VACs with the Apical Membrane Initiation Site (AMIS). Interestingly, VAC fusion at the AMIS was again coordinated with the formation of cell-cell junctions.
Interestingly, our time-resolved proteome revealed distinct recruitment profiles of Rho and Ras GTPases, tight junction membrane and scaffolding proteins, as well as apical proteins, providing new insight into the temporal execution of cell polarity development.
This set of experiments demonstrated that apical lumens are initiated by the exocytosis of large intracellular organelles at nascent cell-cell contact sites. Such organelles contain a pre-assembled microvilli-rich cortex and are known as Vacuolar Apical Compartments (VACs), or apicosomes.
To understand how apical lumen initiation and cell-cell junction assembly are coordinated, we initially analysed polarity development using the calcium switch assay, serial section TEM, and time-resolved proximity proteomics with our favourite enzyme APEX2. This is all done in MDCK cells.
We have some exciting news about how epithelial cells initiate an apical lumen de novo, and how this is coordinated with cell-cell junction formation. Check it out: www.biorxiv.org/content/10.1...
Another beautiful tight junction. This time with scale bar :)
Not bad for a conventionally fixed and dehydrated TEM sample. No HPF/FS. OTO method. Stains the kissing points quite nicely.
