TOPICS 2019
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Yang-Chi-Chun and Hisao Masai (Genome Dynamics Project) published a paper entitled ”Cdc7 activates replication checkpoint by phosphorylating the Chk1 binding domain of Claspin in human cells.” in eLife
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Hikaru Tsuchiya (Laboratory of Protein Metabolism) published a paper entitled “Structural insights into ubiquitin recognition and Ufd1 interaction of Npl4” in Nature Communications.
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Miharu Nakanishi (Mental Health Promotion Project) published a paper entitled ”Midlife Psychological Well-Being and its Impact on Cognitive Functioning Later in Life: An Observational Study Using a Female British Cohort.” in Journal of Alzheimer’s Disease
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Dr. Masato Hosokawa (Dementia Research Project) was awarded the Encouragement Award (Best Basic Research) at the Japan Society for Dementia Research Annual Meeting in 2019.
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Tetsuya Hirabayashi (Laboratory of Biomembrane）published a paper entitled "SDR9C7 catalyzes critical dehydrogenation of acylceramides for skin barrier formation" in The Journal of Clinical Investigation
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Yukio Nishimura (Neural Prosthesis Project) published a paper entitled ”Bypassing stroke-damaged neural pathways via a neural interface induces targeted cortical adaptation” in Nature Communications.
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Takahiko Noro (Visual Research Project) published a paper on glaucoma-like degeneration of the visual system in aged marmosets in Scientific Reports.
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Dr. Fumika Koyano (Ubiquitin Project) published a paper on “Parkin‐mediated ubiquitylation redistributes MITOL/March5 from mitochondria to peroxisomes” in EMBO Reports.
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Keisuke Kamimura (Neural Network Project) published a paper entitled ”The HSPG Glypican Regulates Experience-Dependent Synaptic and Behavioral Plasticity by Modulating the Non-Canonical BMP Pathway” in Cell Reports
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Takahiro Sanada (Viral Infectious Diseases Project) published a paper on “Construction of complete Tupaia belangeri transcriptome database by whole-genome and comprehensive RNA sequencing” in Scientific Reports
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Yuki Nakayama (ALS Nursing Care Project) published a paper on “Body weight variation predicts disease progression after invasive ventilation in amyotrophic lateral sclerosis” in Scientific Reports
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Kazuhiko Namekata (Visual Research Project) published a paper on the role of DOCK8 during neurodegeneration in Journal of Biological Chemistry.
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Daisuke Yamane (Viral Infectious Diseases Project) published a paper on “Basal Expression of Interferon Regulatory Factor 1 Drives Intrinsic Hepatocyte Resistance to Multiple RNA Viruses” in Nature Microbiology
HOME ＞ Topics2019 ＞ 6 November 2019
6 November 2019
Tetsuya Hirabayashi (Laboratory of Biomembrane) published a paper entitled "SDR9C7 catalyzes critical dehydrogenation of acylceramides for skin barrier formation" in The Journal of Clinical Investigation
SDR9C7 catalyzes critical dehydrogenation of acylceramides for skin barrier formation
- ＜Title of the paper＞
- SDR9C7 catalyzes critical dehydrogenation of acylceramides for skin barrier formation
- ＜Journal＞
- The Journal of Clinical Investigation
DOI: 10.1172/JCI130675
https://www.jci.org/articles/view/130675
Summary
Prof. Masashi Akiyama, Dr. Takuya Takeichi at Department of Dermatology, Nagoya University Graduate School of Medicine*, Prof. Alan R. Brash at Department of Pharmacology and the Vanderbilt Institute of Chemical Biology, Vanderbilt University, and Dr. Tetsuya Hirabayashi at Laboratory of Biomembrane, Tokyo Metropolitan Institute of Medical Science, discovered that SDR9C7 catalyzes critical dehydrogenation of acylceramides for skin barrier formation.
SDR9C7 encodes a short chain dehydrogenase/reductase family 9C member 7 (SDR9C7), recently found mutated in ichthyosis. In a patient with SDR9C7 mutation and a mouse Sdr9c7 knockout model, we showed loss of covalent binding of epidermal ceramides to protein, a structural fault in the corneocyte lipid envelope essential to the skin barrier. For reasons unresolved, protein binding requires lipoxygenase-catalyzed transformations of linoleic acid (18:2) esterified in ω-O-acylceramides. In Sdr9c7–/– epidermis, quantitative LC-MS assays revealed almost complete loss of a species of ω-O-acylceramides esterified with linoleate-9,10-trans-epoxy-11E-13-ketone; other acylceramides related to the lipoxygenase pathway were in higher abundance. Recombinant SDR9C7 catalyzed NAD+-dependent dehydrogenation of linoleate 9,10-trans-epoxy-11E-13-alcohol to the corresponding 13-ketone, while ichthyosis mutants were inactive. We propose, therefore, that the critical requirement for lipoxygenases and SDR9C7 is in producing acylceramide containing the 9,10-epoxy-11E-13-ketone, a reactive moiety known for its non-enzymatic coupling to protein. This suggests a novel mechanism for coupling of ceramide to protein and provides important insights into skin barrier formation and ichthyosis pathogenesis.
Research Background
The corneocyte lipid envelope composed of covalently bound ceramides and fatty acids is important to the integrity of the permeability barrier in the stratum corneum, and its absence is a prime structural defect in various skin diseases associated with defective skin barrier function. In 2016, two missense mutations in SDR9C7 were identified in patients with autosomal recessive congenital ichthyosis (ARCI), and several more in 2018. SDR9C7 encodes a short chain dehydrogenase/reductase family 9C member 7 (SDR9C7), and is highly expressed in the epidermis. Our ultrastructural observations of the skin lesion of an ARCI patient with SDR9C7 mutations revealed disruption of the intercellular lipid layers in the stratum corneum.
Research Results
In a patient with SDR9C7 mutation and a mouse Sdr9c7 knockout model, we showed loss of covalent binding of epidermal ceramides to protein, a structural fault in the corneocyte lipid envelope essential to the skin barrier. For reasons unresolved, protein binding requires lipoxygenase-catalyzed transformations of linoleic acid (18:2) esterified in ω-O-acylceramides. In Sdr9c7–/– epidermis, quantitative LC-MS assays revealed almost complete loss of a species of ω-O-acylceramides esterified with linoleate-9,10-trans-epoxy-11E-13-ketone; other acylceramides related to the lipoxygenase pathway were in higher abundance. Recombinant SDR9C7 catalyzed NAD+-dependent dehydrogenation of linoleate 9,10-trans-epoxy-11E-13-alcohol to the corresponding 13-ketone, while ichthyosis mutants were inactive.
Research Summary and Future Perspective
We propose that the critical requirement for lipoxygenases and SDR9C7 is in producing acylceramide containing the 9,10-trans-epoxy-11E-13-ketone, a reactive moiety known for its non-enzymatic coupling to protein. This suggests a mechanism for coupling of ceramide to protein and provides important insights into skin barrier formation and ichthyosis pathogenesis.
Publication
Takuya Takeichi, Tetsuya Hirabayashi, Yuki Miyasaka, Akane Kawamoto, Yusuke Okuno, Shijima Taguchi, Kana Tanahashi, Chiaki Murase, Hiroyuki Takama, Kosei Tanaka, William E. Boeglin, M. Wade Calcutt, Daisuke Watanabe, Michihiro Kono, Yoshinao Muro, Junko Ishikawa, Tamio Ohno, Alan R. Brash, Masashi Akiyama. SDR9C7 catalyzes critical dehydrogenation of acylceramides for skin barrier formation. The Journal of Clinical Investigation, published online before print October 31, 2019.
Laboratory of Biomembrane ▶
* Nagoya University Graduate School of Medicine 
