Epidermal lamellar bodies, essential organelles for the skin barrier

Abstract

Skin lamellar bodies are members of the Lysosome-Related-Organelle (LRO) family, characterized by specific features related to the skin's primary function, i.e., protecting the body from external assaults while minimizing dehydration. In the uppermost living cell layers of the epidermis, the vesicles and tubulovesicular network that make up the « lamellar body system » as identified by electron microscopists, play a crucial role in maintaining the skin barrier. As a secretory compartment, lamellar bodies carry a variety of compounds that, when released in the extracellular space or exposed at the membrane, contribute to the unique hydrophobic structure of the upper epidermis (lipids and lipid metabolism enzymes), regulate desquamation (proteases and inhibitors) and provide anti-microbial defense. The molecular machinery involved in the biogenesis and trafficking of skin lamellar bodies is only beginning to be deciphered, including the Rab11A GTPase, the Myosin5B molecular motor, and the CHEVI complex. This later one is constituted of the Vps33B and VIPAR tethering molecules, whose mutations lead to the ARC and ARKID syndromes. Further studies are needed to identify the key molecules regulating the various stages of LB biogenesis, maturation and exocytosis. It is likely that some of these molecules will be shared with other members of the LRO family. These studies will further enhance our understanding of the relationships between lamellar body trafficking and skin barrier dysfunction.

Keywords: barrier; epidermis; skin; traffic; vesicle.

FIGURE 1

Lamellar bodies in multilayered epidermis. The epidermis is primarily constituted of keratinocytes, organized in various cell layers undergoing orderly differentiation. A melanocyte (brown cell) and a Langerhans cell (light brown cell) are also present in the epithelium. Lamellar bodies (yellow circles) are shown in keratinocytes of the Stratum Granulosum (SG) (left picture made with bioRender). By transmission electron microscopy, lamellar bodies can be observed at different scales: electron micrographs in the right part of the figure have been acquired by C. Leprince, from human skin biopsies as described in Reynier et al. (2019). Briefly, skin biopsies have been fixed with a mix of glutaraldehyde and paraformaldehyde, post-fixed with osmium tetroxyde, embedded in epoxy resin and post stained with uranyl acetate and lead citrate.

FIGURE 2

Diversity of lamellar body cargoes and related functions. The LB components detailed above come from data published by Wertz (2018), Wertz et al. (1984), Grayson et al. (1985), Vietri and Watt (2022) for the lipid part, and (Raymond et al., 2008) for the protein part. Components were grouped according to their biological function (picture made with bioRender).

FIGURE 3

Control of LB trafficking in granular keratinocytes by the Rab11A GTPase, the Myosin 5B molecular motor and the CHEVI tethering compex (picture made with bioRender).