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

Justin C. Rudd, Jos P. H. Smits, Patrick T. Kuwong, Rachel E. Johnson, Louise M. N. Monga, Ivonne M. J. J. Vlijmen-Willems, Greer L. Porter, Peter O. Halloran, Kanika Sharma, Karina N. Schmidt, Vikas Kumar, Justin G. Madson, Mrinal K. Sarkar, Ellen H. Bogaard, James A. Grunkemeyer, Johann E. Gudjonsson, Sunny Y. Wong, Cory L. Simpson and Laura A. Hansen ()
Additional contact information
Justin C. Rudd: Creighton University School of Medicine
Jos P. H. Smits: Radboud Research Institute for Medical Innovation
Patrick T. Kuwong: Creighton University School of Medicine
Rachel E. Johnson: Creighton University School of Medicine
Louise M. N. Monga: Creighton University School of Medicine
Ivonne M. J. J. Vlijmen-Willems: Radboud Research Institute for Medical Innovation
Greer L. Porter: Creighton University School of Medicine
Peter O. Halloran: Creighton University School of Medicine
Kanika Sharma: University of Nebraska Medical Center
Karina N. Schmidt: University of Washington
Vikas Kumar: University of Nebraska Medical Center
Justin G. Madson: Midwest Dermatology
Mrinal K. Sarkar: University of Michigan
Ellen H. Bogaard: Radboud Research Institute for Medical Innovation
James A. Grunkemeyer: Creighton University School of Medicine
Johann E. Gudjonsson: University of Michigan
Sunny Y. Wong: University of Michigan
Cory L. Simpson: University of Washington
Laura A. Hansen: Creighton University School of Medicine

Nature Communications, 2025, vol. 16, issue 1, 1-19

Abstract: 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.

Date: 2025
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-62105-1 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-62105-1

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-62105-1

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().