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<p>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 Ca<sup>2+</sup> 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 Ca<sup>2+</sup> 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 Ca<sup>2+</sup> 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 Ca<sup>2+</sup> dependency to distinct stages of the transport process depending on the cell of origin.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年7月26日

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  • 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

摘要

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.