Flower dependent trafficking of lamellar bodies facilitates maturation of the epidermal barrier

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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Main Authors: 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
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-62105-1
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Summary: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.
ISSN:2041-1723

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