Flower dependent trafficking of lamellar bodies facilitates maturation of the epidermal barrier
Abstract Specialized secretory cells, including keratinocytes in the last viable layers of mammalian epidermis, utilize lysosome-related organelles (LROs) to exocytose distinct cargoes vital for tissue function. Here, we demonstrate that the Flower isoform, hFWE4, a putative Ca2+ channel that permit...
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Nature Portfolio
2025-07-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-62105-1 |
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| author | Justin C. Rudd Jos P. H. Smits Patrick T. Kuwong Rachel E. Johnson Louise M. N. Monga Ivonne M. J. J. van Vlijmen-Willems Greer L. Porter Peter O. Halloran Kanika Sharma Karina N. Schmidt Vikas Kumar Justin G. Madson Mrinal K. Sarkar Ellen H. van den Bogaard James A. Grunkemeyer Johann E. Gudjonsson Sunny Y. Wong Cory L. Simpson Laura A. Hansen |
| author_facet | Justin C. Rudd Jos P. H. Smits Patrick T. Kuwong Rachel E. Johnson Louise M. N. Monga Ivonne M. J. J. van Vlijmen-Willems Greer L. Porter Peter O. Halloran Kanika Sharma Karina N. Schmidt Vikas Kumar Justin G. Madson Mrinal K. Sarkar Ellen H. van den Bogaard James A. Grunkemeyer Johann E. Gudjonsson Sunny Y. Wong Cory L. Simpson Laura A. Hansen |
| author_sort | Justin C. Rudd |
| collection | DOAJ |
| description | Abstract Specialized secretory cells, including keratinocytes in the last viable layers of mammalian epidermis, utilize lysosome-related organelles (LROs) to exocytose distinct cargoes vital for tissue function. Here, we demonstrate that the Flower isoform, hFWE4, a putative Ca2+ channel that permits endocytic retrieval of presynaptic vesicles and lytic granules, also resides on epidermal lamellar bodies (LBs), an LRO that extrudes a proteinaceous lipid-rich matrix to finalize the epidermal barrier. In differentiated keratinocyte cultures, we show that hFWE4-positive LB-like vesicles associate with a distinct ensemble of LRO trafficking mediators and demonstrate that hFWE4 liberates Ca2+ from intracellular stores to enable the surface presentation of cargo contained within these vesicles. Finally, supporting a critical role for hFWE4-dependent trafficking in establishing the epidermal barrier, we demonstrate that this process is dysregulated in genetic diseases of cornification that are driven by impairments in keratinocyte Ca2+ handling. Our results provide new insight into the biogenesis and trafficking of epidermal LBs and more broadly suggest that hFWE4 may serve as a core component of LRO trafficking machinery that endows Ca2+ dependency to distinct stages of the transport process depending on the cell of origin. |
| format | Article |
| id | doaj-art-532aac7a1ca34c04b267ee5d1a81b763 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-532aac7a1ca34c04b267ee5d1a81b7632025-08-20T04:02:54ZengNature PortfolioNature Communications2041-17232025-07-0116111910.1038/s41467-025-62105-1Flower dependent trafficking of lamellar bodies facilitates maturation of the epidermal barrierJustin C. Rudd0Jos P. H. Smits1Patrick T. Kuwong2Rachel E. Johnson3Louise M. N. Monga4Ivonne M. J. J. van Vlijmen-Willems5Greer L. Porter6Peter O. Halloran7Kanika Sharma8Karina N. Schmidt9Vikas Kumar10Justin G. Madson11Mrinal K. Sarkar12Ellen H. van den Bogaard13James A. Grunkemeyer14Johann E. Gudjonsson15Sunny Y. Wong16Cory L. Simpson17Laura A. Hansen18Department of Biomedical Sciences, Creighton University School of MedicineDepartment of Dermatology, Radboud Research Institute for Medical InnovationDepartment of Biomedical Sciences, Creighton University School of MedicineDepartment of Biomedical Sciences, Creighton University School of MedicineDepartment of Biomedical Sciences, Creighton University School of MedicineDepartment of Dermatology, Radboud Research Institute for Medical InnovationDepartment of Biomedical Sciences, Creighton University School of MedicineDepartment of Biomedical Sciences, Creighton University School of MedicineMass Spectrometry and Proteomics Core Facility, University of Nebraska Medical CenterDepartment of Dermatology, University of WashingtonMass Spectrometry and Proteomics Core Facility, University of Nebraska Medical CenterMidwest DermatologyDepartment of Dermatology, University of MichiganDepartment of Dermatology, Radboud Research Institute for Medical InnovationDepartment of Biomedical Sciences, Creighton University School of MedicineDepartment of Dermatology, University of MichiganDepartment of Dermatology, University of MichiganDepartment of Dermatology, University of WashingtonDepartment of Biomedical Sciences, Creighton University School of MedicineAbstract Specialized secretory cells, including keratinocytes in the last viable layers of mammalian epidermis, utilize lysosome-related organelles (LROs) to exocytose distinct cargoes vital for tissue function. Here, we demonstrate that the Flower isoform, hFWE4, a putative Ca2+ channel that permits endocytic retrieval of presynaptic vesicles and lytic granules, also resides on epidermal lamellar bodies (LBs), an LRO that extrudes a proteinaceous lipid-rich matrix to finalize the epidermal barrier. In differentiated keratinocyte cultures, we show that hFWE4-positive LB-like vesicles associate with a distinct ensemble of LRO trafficking mediators and demonstrate that hFWE4 liberates Ca2+ from intracellular stores to enable the surface presentation of cargo contained within these vesicles. Finally, supporting a critical role for hFWE4-dependent trafficking in establishing the epidermal barrier, we demonstrate that this process is dysregulated in genetic diseases of cornification that are driven by impairments in keratinocyte Ca2+ handling. Our results provide new insight into the biogenesis and trafficking of epidermal LBs and more broadly suggest that hFWE4 may serve as a core component of LRO trafficking machinery that endows Ca2+ dependency to distinct stages of the transport process depending on the cell of origin.https://doi.org/10.1038/s41467-025-62105-1 |
| spellingShingle | Justin C. Rudd Jos P. H. Smits Patrick T. Kuwong Rachel E. Johnson Louise M. N. Monga Ivonne M. J. J. van Vlijmen-Willems Greer L. Porter Peter O. Halloran Kanika Sharma Karina N. Schmidt Vikas Kumar Justin G. Madson Mrinal K. Sarkar Ellen H. van den Bogaard James A. Grunkemeyer Johann E. Gudjonsson Sunny Y. Wong Cory L. Simpson Laura A. Hansen Flower dependent trafficking of lamellar bodies facilitates maturation of the epidermal barrier Nature Communications |
| title | Flower dependent trafficking of lamellar bodies facilitates maturation of the epidermal barrier |
| title_full | Flower dependent trafficking of lamellar bodies facilitates maturation of the epidermal barrier |
| title_fullStr | Flower dependent trafficking of lamellar bodies facilitates maturation of the epidermal barrier |
| title_full_unstemmed | Flower dependent trafficking of lamellar bodies facilitates maturation of the epidermal barrier |
| title_short | Flower dependent trafficking of lamellar bodies facilitates maturation of the epidermal barrier |
| title_sort | flower dependent trafficking of lamellar bodies facilitates maturation of the epidermal barrier |
| url | https://doi.org/10.1038/s41467-025-62105-1 |
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