Unbound Corneocyte Lipid Envelopes in 12R-Lipoxygenase Deficiency Support a Specific Role in Lipid-Protein Cross-Linking
Meyer JM, Crumrine D, Schneider H, Dick A, Schmuth M, Gruber R, Radner FP, Grond S, Wakefield JS, Mauro TM, Elias PM (2021)
Publication Type: Journal article
Publication year: 2021
Journal
Book Volume: 191
Pages Range: 921-929
Journal Issue: 5
DOI: 10.1016/j.ajpath.2021.02.005
Abstract
Loss-of-function mutations in arachidonate lipoxygenase 12B (ALOX12B) are an important cause of autosomal recessive congenital ichthyosis (ARCI). 12R-lipoxygenase (12R-LOX), the protein product of ALOX12B, has been proposed to covalently bind the corneocyte lipid envelope (CLE) to the proteinaceous corneocyte envelope, thereby providing a scaffold for the assembly of barrier-providing, mature lipid lamellae. To test this hypothesis, an in-depth ultrastructural examination of CLEs was performed in ALOX12B−/− human and Alox12b−/− mouse epidermis, extracting samples with pyridine to distinguish covalently attached CLEs from unbound (ie, noncovalently bound) CLEs. ALOX12B−−/− stratum corneum contained abundant pyridine-extractable (ie, unbound) CLEs, compared with normal stratum corneum. These unbound CLEs were associated with defective post-secretory lipid processing, and were specific to 12R-LOX deficiency, because they were not observed with deficiency of the related ARCI-associated proteins, patatin-like phospholipase 1 (Pnpla1) or abhydrolase domain containing 5 (Abhd5). These results suggest that 12R-LOX contributes specifically to CLE–corneocyte envelope cross-linking, which appears to be a prerequisite for post-secretory lipid processing, and provide insights into the pathogenesis of 12R-LOX deficiency in this subtype of ARCI, as well as other conditions that display a defective CLE.
Authors with CRIS profile
Holm Schneider
Professur für Kinderheilkunde/Experimentelle Perinatalmedizin
Angela Dick
Lehrstuhl für Genetik
Involved external institutions
Medizinische Universität Innsbruck
Austria (AT)
Karl-Franzens-Universität Graz
Austria (AT)
San Francisco VA Medical Center (SFVAMC) / San Francisco Veterans Affairs Medical Center
United States (USA) (US)
University of California San Francisco (UCSF)
United States (USA) (US)
Austria (AT)
Karl-Franzens-Universität Graz
Austria (AT)
San Francisco VA Medical Center (SFVAMC) / San Francisco Veterans Affairs Medical Center
United States (USA) (US)
University of California San Francisco (UCSF)
United States (USA) (US)
How to cite
APA:
Meyer, J.M., Crumrine, D., Schneider, H., Dick, A., Schmuth, M., Gruber, R.,... Elias, P.M. (2021). Unbound Corneocyte Lipid Envelopes in 12R-Lipoxygenase Deficiency Support a Specific Role in Lipid-Protein Cross-Linking. American Journal of Pathology, 191(5), 921-929. https://dx.doi.org/10.1016/j.ajpath.2021.02.005
MLA:
Meyer, Jason M., et al. "Unbound Corneocyte Lipid Envelopes in 12R-Lipoxygenase Deficiency Support a Specific Role in Lipid-Protein Cross-Linking." American Journal of Pathology 191.5 (2021): 921-929.
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