Secretion Bias of Lamellar Granules Revealed by Three-Dimensional Electron Microscopy.

Lamellar granules (LGs) or lamellar bodies in the epidermis are important cell organelles whose contents are secreted extracellularly and contribute to the skin barrier function ( Elias and Wakefield, 2014 Elias P.M. Wakefield J.S. Mechanisms of abnormal lamellar body secretion and the dysfunctional skin barrier in patients with atopic dermatitis. J Allergy Clin Immunol. 2014; 134: 781-791.e1 Abstract Full Text Full Text PDF PubMed Scopus (158) Google Scholar ). Understanding the secretory mechanisms of LGs is essential to understanding normal skin physiology. Classical electron microscopy (EM) has shown that LGs appear in the spinous layer and that the contents are secreted extracellularly by the fusion of the granule membrane and the cell membrane in the granular layer ( Odland and Holbrook, 1981 Odland G.F. Holbrook K. The lamellar granules of epidermis. Curr Probl Dermatol. 1981; 9: 29-49 Crossref PubMed Google Scholar ). Our earlier three-dimensional (3D) EM studies using focused ion beam scanning EM revealed that LGs remain in the cytoplasm in the third layer below the stratum corneum and that secretion begins in the second granular layer (SG2), and all granules are secreted in the first granular layer (SG1) ( Yamanishi et al., 2019 Yamanishi H. Soma T. Kishimoto J. Hibino T. Ishida-Yamamoto A. Marked changes in lamellar granule and trans-Golgi network structure occur during epidermal keratinocyte differentiation. J Invest Dermatol. 2019; 139: 352-359 Abstract Full Text Full Text PDF PubMed Scopus (13) Google Scholar ). Several molecules are involved in the intracellular trafficking of LGs ( Ishida-Yamamoto et al., 2007 Ishida-Yamamoto A. Kishibe M. Takahashi H. Iizuka H. Rab11 is associated with epidermal lamellar granules. J Invest Dermatol. 2007; 127: 2166-2170 Abstract Full Text Full Text PDF PubMed Scopus (21) Google Scholar ; Reynier et al., 2019 Reynier M. Allart S. Goudounèche D. Moga A. Serre G. Simon M. et al. The actin-based motor myosin Vb is crucial to maintain epidermal barrier integrity. J Invest Dermatol. 2019; 139: 1430-1438 Abstract Full Text Full Text PDF PubMed Scopus (5) Google Scholar , Reynier et al., 2016 Reynier M. Allart S. Gaspard E. Moga A. Goudounèche D. Serre G. et al. Rab11a is essential for lamellar body biogenesis in the human epidermis. J Invest Dermatol. 2016; 136: 1199-1209 Abstract Full Text Full Text PDF PubMed Scopus (21) Google Scholar ; Sando et al., 2003 Sando G.N. Zhu H. Weis J.M. Richman J.T. Wertz P.W. Madison K.C. Caveolin expression and localization in human keratinocytes suggest a role in lamellar granule biogenesis. J Invest Dermatol. 2003; 120: 531-541 Abstract Full Text Full Text PDF PubMed Scopus (44) Google Scholar ). However, details of the regulatory mechanism of trafficking and secretion of LGs still need to be fully elucidated ( Ishida-Yamamoto et al., 2004 Ishida-Yamamoto A. Simon M. Kishibe M. Miyauchi Y. Takahashi H. Yoshida S. et al. Epidermal lamellar granules transport different cargoes as distinct aggregates. J Invest Dermatol. 2004; 122: 1137-1144 Abstract Full Text Full Text PDF PubMed Scopus (120) Google Scholar ; Mahanty and Setty, 2021 Mahanty S. Setty S.R.G. Epidermal lamellar body biogenesis: insight into the roles of Golgi and lysosomes. Front Cell Dev Biol. 2021; 9: 701950 Crossref PubMed Scopus (5) Google Scholar ).