Journal of cell science最新文献

Branched actin segregates endocytic cargo to control sorting and fission. 分支肌动蛋白分离内吞货物以控制分选和裂变。

IF 3.9 3区生物学

Journal of cell science Pub Date : 2026-11-01 Epub Date: 2026-08-25 DOI: 10.1242/jcs.265091

Devin Frisby, Naava Naslavsky, Steve Caplan

{"title":"Branched actin segregates endocytic cargo to control sorting and fission.","authors":"Devin Frisby, Naava Naslavsky, Steve Caplan","doi":"10.1242/jcs.265091","DOIUrl":"10.1242/jcs.265091","url":null,"abstract":"At the early endosome, cargos are sorted into subdomains; receptors destined for recycling to the plasma membrane are sorted into tubulovesicular structures that undergo fission and release cargo-laden vesicles that traffic along microtubules. Although branched actin has been implicated in the establishment and/or maintenance of endosomal membrane subdomains, its role in cargo segregation, fission and recycling has not been extensively studied. Using chemical inhibitors and siRNA knockdown to impede formin- and ARP2/3-mediated actin assembly, we show that branched actin, but not linear actin, is required for endosome fission and receptor recycling. To examine the spatial relationship between actin and cargo, we transfected cells with constitutively active RAB5 Q79L to generate enlarged endosomes and demonstrated that internalized transferrin localized to discrete endosomal regions adjacent to branched actin. ARP2/3 inhibition disrupted this organization, maintaining receptors at the endosome, resulting in broader cargo distribution on the endosomal membrane and coalescence of clathrin-dependent degradative cargo with clathrin-independent recycling cargo. Our findings identify ARP2/3-mediated branched actin as a key regulator of cargo segregation, subdomain maintenance and fission at the early endosome.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148390420","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Potential role of myeloid bodies in protection against photo-oxidative damage of the retinal pigment epithelium. 髓小体在保护视网膜色素上皮免受光氧化损伤中的潜在作用。

IF 3.9 3区生物学

Journal of cell science Pub Date : 2026-11-01 Epub Date: 2026-08-24 DOI: 10.1242/jcs.264938

Iñigo Novales Flamarique

{"title":"Potential role of myeloid bodies in protection against photo-oxidative damage of the retinal pigment epithelium.","authors":"Iñigo Novales Flamarique","doi":"10.1242/jcs.264938","DOIUrl":"10.1242/jcs.264938","url":null,"abstract":"Myeloid bodies are organized forms of the smooth endoplasmic reticulum that occur in the retinal pigment epithelium of vertebrates. The latter is a monolayer of cells, situated between the neural retina and the chroroid vasculature, that is essential for photoreceptor homeostasis and function. Myeloid bodies operate in an environment of high oxygen tension and chronic light exposure where phagocytosis of photoreceptor outer segments takes place, resulting in photo-oxidative stress. Over time, such damage can result in pigment epithelium cell death, retinal degeneration and blindness. The purpose of myeloid bodies is unknown. Here, unusually large myeloid bodies are described, with cisternae perpendicular to the basal epithelium (Bruch's) membrane, that occur throughout the differentiated retina of the sablefish Anoplopoma fimbria, a marine fish with early life history exposure to the full spectrum of light. Immunogold labelling of thin sections was used to demonstrate exclusive cisternal binding of short-wavelength (blue) light-absorbing opsins and a zeaxanthin carotenoid-associated enzyme. Because blue light is highly efficient at inducing photo-oxidation, the sequestration of these compounds within myeloid bodies suggests that the smooth endoplasmic reticulum has an optical role in filtering light to prevent photo-oxidative damage.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148390513","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

OpticalFlow3D - a tool for measuring amorphous motion in three-dimensional fluorescence microscopy images. OpticalFlow3D -测量三维荧光显微镜图像中无定形运动的工具。

IF 3.9 3区生物学

Journal of cell science Pub Date : 2026-11-01 Epub Date: 2026-07-15 DOI: 10.1242/jcs.264851

Rachel M Lee, Leanna R Eisenman, Chad M Hobson, Jesse S Aaron, Teng-Leong Chew

{"title":"OpticalFlow3D - a tool for measuring amorphous motion in three-dimensional fluorescence microscopy images.","authors":"Rachel M Lee, Leanna R Eisenman, Chad M Hobson, Jesse S Aaron, Teng-Leong Chew","doi":"10.1242/jcs.264851","DOIUrl":"10.1242/jcs.264851","url":null,"abstract":"Motion is an essential component of any living system. It is rich with information, but it is often challenging to quantitatively extract biologically informative results from the motion apparent in microscopy images. This challenge is exacerbated by the wide variety in biological movement, which often takes the form of difficult-to-segment amorphous structures undergoing complex motion. An image processing technique known as optical flow can capture motion at each pixel in an image, thus bypassing the need for object segmentation or prior definition of motion types. This makes it a powerful tool for quantitative assessment of biological systems from the protein to organism scale. However, despite its flexibility and strengths for analyzing fluorescence microscopy images, its adoption in the bioimaging community has been limited by the availability of easy-to-use tools and guidance in results interpretation. Here, we describe an optical flow tool, called OpticalFlow3D, that can be run in Python or MATLAB and is compatible with three-dimensional microscopy images. Using biological examples across length scales, we illustrate how OpticalFlow3D can enable new biological insight.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":"139 21","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13405222/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148446993","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cooperative definition of ER exit sites by Tango1, Sec16 and Sec12. Tango1、Sec16和Sec12协同定义ER出口位点。

IF 3.9 3区生物学

Journal of cell science Pub Date : 2026-11-01 Epub Date: 2026-09-29 DOI: 10.1242/jcs.264950

Zhi Feng, Mercedes Martín, Marta Rojas, José Carlos Pastor-Pareja

{"title":"Cooperative definition of ER exit sites by Tango1, Sec16 and Sec12.","authors":"Zhi Feng, Mercedes Martín, Marta Rojas, José Carlos Pastor-Pareja","doi":"10.1242/jcs.264950","DOIUrl":"10.1242/jcs.264950","url":null,"abstract":"Endoplasmic reticulum (ER) exit sites (ERES) are dynamic ER subdomains where secretory cargos are concentrated and exported towards the Golgi. The conserved proteins Sec16 and Sec12 have long been implicated in ERES organization, whereas animal-specific Tango1 has more recently emerged as a possible additional determinant. Their respective roles in ERES morphogenesis, however, remain unclear. Using Drosophila, we dissect the mutual requirements and specific functions of Sec16, Sec12 and Tango1 in defining ERES. We show that Sec16 and Tango1 are interdependent for proper ERES assembly, with co-overexpression producing exaggerated ERES structures. We further identify CG9175 as the Drosophila ortholog of Sec12 and demonstrate its upstream requirement for coordinated concentration of Tango1 and Sec16. Tango1 is in turn important for ERES-Golgi coupling. Finally, both Tango1 and Sec16 are required for concentration of COPII and COPI components, albeit with different relative impacts. Together, our findings support the evolutionary incorporation of Tango1 into a cooperative network in which Sec12, Sec16 and Tango1 make distinct contributions to the definition of animal ERES.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148664016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

DySTrack - a modular smart microscopy tool for live tracking of dynamic samples on modern commercial microscopes. DySTrack：一个模块化的智能显微镜工具，用于实时跟踪现代商业显微镜上的动态样品。

IF 3.9 3区生物学

Journal of cell science Pub Date : 2026-11-01 Epub Date: 2026-05-26 DOI: 10.1242/jcs.264728

Zimeng Wu, Octavian Voiculescu, Alessandro Mongera, Roberto Mayor, Mie Wong, Jonas Hartmann

{"title":"DySTrack - a modular smart microscopy tool for live tracking of dynamic samples on modern commercial microscopes.","authors":"Zimeng Wu, Octavian Voiculescu, Alessandro Mongera, Roberto Mayor, Mie Wong, Jonas Hartmann","doi":"10.1242/jcs.264728","DOIUrl":"10.1242/jcs.264728","url":null,"abstract":"Advances in microscopy and bioimage analysis are enabling unprecedented quantitative observation of dynamic biological systems. Smart microscopy closes the loop by feeding back image-derived information to control image acquisition on the fly, paving the way for increasingly autonomous and sophisticated experiments. However, adoption of smart microscopy remains limited primarily to specialists, and even simple tasks such as live tracking of moving samples are still widely handled manually. Here, we describe DySTrack, a modular open-source Python tool that serves as a minimal bridge between commercial acquisition software and arbitrary image analysis pipelines, allowing users to stick with familiar vendor-developed user interfaces for microscope configuration while leveraging the powerful and platform-agnostic Python ecosystem for image analysis. DySTrack comes with detailed documentation and with ready-to-use, easy-to-adapt example pipelines that track moving tissues (namely the zebrafish lateral line primordium and the chick Hensen's node) during embryonic development. We hope DySTrack will contribute to a recent push to make smart microscopy more widely accessible.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13286349/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147772616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

FGD1 restrains actomyosin contractility to promote suprabasal junction maturation in stratified keratinocytes. FGD1抑制肌动球蛋白收缩以促进层状角质形成细胞的基底上结成熟。

IF 3.9 3区生物学

Journal of cell science Pub Date : 2026-11-01 Epub Date: 2026-09-23 DOI: 10.1242/jcs.264937

Diana I Hotea, Alexandra Jetté, Amy Beaudin, Maité Lauzon, Krithika Kalyanakrishnan, Mélanie Laurin

{"title":"FGD1 restrains actomyosin contractility to promote suprabasal junction maturation in stratified keratinocytes.","authors":"Diana I Hotea, Alexandra Jetté, Amy Beaudin, Maité Lauzon, Krithika Kalyanakrishnan, Mélanie Laurin","doi":"10.1242/jcs.264937","DOIUrl":"10.1242/jcs.264937","url":null,"abstract":"The epidermis is a stratified epithelium in which keratinocytes differentiate as they move from basal to suprabasal layers, a process during which tissue integrity relies on the coordinated remodeling of intercellular junctions and the cytoskeleton. Unlike simple epithelia, which form a continuous zonula adherens, suprabasal cells in the epidermis lack a canonical junction belt, with E-cadherin-based junctions distributed across the entire cell surface, highlighting distinct regulatory mechanisms that remain poorly understood. Here, we identify the CDC42 guanine nucleotide exchange factor FGD1, mutated in Aarskog-Scott syndrome, as a regulator of suprabasal junction architecture. Using stratified human keratinocytes and quantitative imaging, we show that loss of FGD1 induces elongated radial actin bundles and tortuous, tension-associated adherens junctions resembling the stress fiber-anchored discontinuous (focal) adherens junctions described in endothelial cells. These defects are accompanied by altered tissue mechanics. Inhibition of ROCK or myosin II restores junction organization, demonstrating that FGD1 restrains actomyosin contractility to promote suprabasal junction maturation. Several disease-associated FGD1 variants fail to rescue these defects. Together, our findings identify FGD1 as a regulator of suprabasal junction maturation.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148684646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

TGF-β signaling modulates adhesion and actomyosin contractility to pattern epithelial permeability in Drosophila ovaries. TGF-β信号调节果蝇卵巢黏附和肌动球蛋白收缩，从而影响上皮通透性。

IF 3.9 3区生物学

Journal of cell science Pub Date : 2026-11-01 Epub Date: 2026-10-12 DOI: 10.1242/jcs.264997

Harshath Amal, Thea Jacobs, Max Lohrberg, Stefan Luschnig

{"title":"TGF-β signaling modulates adhesion and actomyosin contractility to pattern epithelial permeability in Drosophila ovaries.","authors":"Harshath Amal, Thea Jacobs, Max Lohrberg, Stefan Luschnig","doi":"10.1242/jcs.264997","DOIUrl":"10.1242/jcs.264997","url":null,"abstract":"Epithelial morphogenesis and homeostasis depend on dynamic remodeling of cell-cell junctions. Tricellular junctions (TCJs) control epithelial permeability and plasticity, yet how TCJs are remodeled remains unclear. In the Drosophila ovarian follicular epithelium, TCJs open transiently in a process called patency to allow passage of yolk proteins for uptake by the oocyte. Here, we investigated how a TGF-β signaling gradient represses patency along the follicular epithelium. We show that TGF-β signaling blocks patency cell-autonomously by strengthening E-Cadherin (E-Cad, also known as Shg)-based adhesion through inducing E-Cad transcription and preventing E-Cad removal from vertices. Elevated E-Cad levels alone were not sufficient to block patency, implying that additional TGF-β-dependent mechanisms stabilize E-Cad at vertices. We identify p120-catenin (p120ctn) upregulation as a mechanism that may contribute to strengthened adhesion. In parallel, TGF-β signaling activates myosin II through Rho-Rok signaling. However, myosin II activity is dispensable for TGF-β-mediated patency suppression. Thus, our findings suggest that TGF-β signaling controls TCJ remodeling in follicle cells primarily by reinforcing E-Cad-based adhesion, disentangling the roles of adhesion and actomyosin contractility in maintaining TCJ integrity and revealing how a morphogen gradient spatially patterns epithelial permeability.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148722011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

NucleiSky enables cross-scale multimodal registration of microscopy data using nuclei constellations. NucleiSky使用核星座实现显微镜数据的跨尺度多模态配准。

IF 3.9 3区生物学

Journal of cell science Pub Date : 2026-11-01 Epub Date: 2026-10-14 DOI: 10.1242/jcs.265152

Iván Hidalgo-Cenalmor, Adán Olguín-Olguín, Carolina Prieto, Johannes Kumra Ahnlide, Pontus Nordenfelt, Ricardo Henriques, Mario Del Rosario, Guillaume Jacquemet

{"title":"NucleiSky enables cross-scale multimodal registration of microscopy data using nuclei constellations.","authors":"Iván Hidalgo-Cenalmor, Adán Olguín-Olguín, Carolina Prieto, Johannes Kumra Ahnlide, Pontus Nordenfelt, Ricardo Henriques, Mario Del Rosario, Guillaume Jacquemet","doi":"10.1242/jcs.265152","DOIUrl":"10.1242/jcs.265152","url":null,"abstract":"Integrating tissue-level organisation with subcellular resolution and molecular information often requires combining multiple microscopy modalities and scales. However, aligning images acquired with different modalities, settings or instruments remains challenging. Here, we introduce NucleiSky, a microscopy image registration framework that utilises the spatial arrangement of nuclei or other landmarks as an intrinsic biological fingerprint. NucleiSky represents images as constellations of centroids and aligns them using geometric algorithms and spatial consensus scoring. In benchmark datasets, NucleiSky could localise query regions within larger reference images using as few as five nuclei. We show that NucleiSky can locate high-magnification fields of view within low-magnification overview scans, map these alignments to additional channels, support live brightfield-to-fixed registration using synthetic nuclear labels and guide microscope re-targeting. We further show that the same constellation-matching principle can be extended to 3D localisation and to non-nuclear landmarks. These findings establish local landmark geometry as an intrinsic spatial fingerprint that enables localisation and registration across imaging scales, modalities and microscopy platforms. NucleiSky is available as an open-source Python package and as notebook-based applications.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148759003","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Identification of feeding apparatus components in a heterotrophic marine flagellate. 异养海洋鞭毛虫摄食器官组成的鉴定。

IF 3.9 3区生物学

Journal of cell science Pub Date : 2026-11-01 Epub Date: 2026-09-18 DOI: 10.1242/jcs.264933

Gillian Clifford, Samuel J P Taylor, Midori Ishii, Fernanda Cisneros-Soberanis, Bungo Akiyoshi

{"title":"Identification of feeding apparatus components in a heterotrophic marine flagellate.","authors":"Gillian Clifford, Samuel J P Taylor, Midori Ishii, Fernanda Cisneros-Soberanis, Bungo Akiyoshi","doi":"10.1242/jcs.264933","DOIUrl":"10.1242/jcs.264933","url":null,"abstract":"Diplonemids are highly abundant heterotrophic single-celled flagellates that are widespread throughout the oceans of the world. They have a highly complex microtubule-based feeding apparatus (the cytostome-cytopharynx complex) located adjacent to the deep flagellar pocket from which two flagella emerge. The apical papilla is a tongue-shaped structure unique to diplonemids that connects the cytopharynx and the flagellar pocket, the latter of which is formed by reinforcing microtubules (MTR) and two flagellar roots called intermediate and dorsal roots. Here, we report identification of 17 proteins that localize at the feeding apparatus or flagellar apparatus in Diplonema papillatum. Using ultrastructure expansion microscopy, we show that Mad2 and its interaction partner MBP65 localize at the MTR, intermediate root and dorsal root. Homologs of proteins that associate with the flagellar apparatus in Trypanosoma brucei (PFR2, KMP-11 and BILBO1) localize at the feeding apparatus in D. papillatum. We also identify proteins that localize at the apical papilla, MTR, parallel microtubule loop and cytopharynx. By discovering many components of the feeding apparatus in diplonemids, this work forms the foundation to understand the feeding mechanism in these highly abundant marine planktonic organisms.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13615690/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148684651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cell surface remodeling caused by the loss of the flippase subunit TMEM30A in immune cells. 免疫细胞中翻转酶亚基TMEM30A缺失引起的细胞表面重塑

IF 3.9 3区生物学

Journal of cell science Pub Date : 2026-11-01 Epub Date: 2026-08-14 DOI: 10.1242/jcs.264813

Cenk O Gurdap, Franziska Ragaller, Marion Muller, Ellen Sjule, Taras Sych, Linnea Blomén, Fredrik B Thorén, Ilya Levental, Kandice R Levental, Quentin J Sattentau, Erdinc Sezgin

{"title":"Cell surface remodeling caused by the loss of the flippase subunit TMEM30A in immune cells.","authors":"Cenk O Gurdap, Franziska Ragaller, Marion Muller, Ellen Sjule, Taras Sych, Linnea Blomén, Fredrik B Thorén, Ilya Levental, Kandice R Levental, Quentin J Sattentau, Erdinc Sezgin","doi":"10.1242/jcs.264813","DOIUrl":"10.1242/jcs.264813","url":null,"abstract":"Plasma membrane lipid asymmetry is tightly regulated and fundamental to mammalian cell physiology. TMEM30A is the β-subunit of P4-ATPases, flippase enzymes that maintain strict phosphatidylserine (PS) asymmetry by pumping it from the outer to the cytosolic leaflet. Loss of TMEM30A function causes constitutive PS externalization and has been implicated in diseases such as diffuse large B-cell lymphoma and tumor immune evasion. Here, we systematically define the biophysical and molecular consequences of TMEM30A deletion in immune cells. Using a live-cell lipid reporter, membrane order probe, and surface proteome mapping, we show that TMEM30A-knockout cells display robust PS externalization accompanied by faster lateral diffusion of membrane constituents and decreased plasma membrane order. Surface proteome reorganization includes increased abundance of tetraspanins and CD47. Furthermore, TMEM30A loss triggers glycocalyx remodeling via ADAM10-dependent shedding, which removes major transmembrane mucins, including CD43 and CD162 (also known as SPN and SELPLG, respectively). Together, these data reveal a coordinated reorganization of lipids, glycans and proteins upon TMEM30A loss, suggesting mechanistic links between flippase dysfunction and increased plasma membrane dynamics and potential sensitization to immune therapy. Furthermore, our study provides an integrated surfaceome framework that might shed light on the relationship between TMEM30A expression and clinical outcomes in cancer.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":"139 21","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13535326/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148764647","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0