Naked mole-rat TMEM2 lacks physiological hyaluronan-degrading activity.

Autor: Sato S; Department of Cosmetic Health Science, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu, 501-1196, Japan; TOA Inc., Nippon Life Yodoyabashi Bldg., 17F, 3-5-29, Kitahama, Chuo-ku, Osaka, 541-0041, Japan., Mizutani Y; Department of Cosmetic Health Science, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu, 501-1196, Japan., Abe M; Department of Cosmetic Health Science, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu, 501-1196, Japan., Fukuda S; Department of Biochemistry, School of Dentistry, Aichi Gakuin University, 1-100 Kusumoto-cho, Chikusaku, Nagoya, Aichi, 464-8650, Japan., Higashiyama S; Department of Cell Growth and Tumor Regulation, Proteo-Science Center, Ehime University, Shitsukawa, Toon, Ehime, 791-0295, Japan; Department of Biochemistry and Molecular Genetics, Graduate School of Medicine, Ehime University, Shitsukawa, Toon, Ehime, 791-0295, Japan; Department of Oncogenesis and Growth Regulation, Osaka International Cancer Institute, 3-1-69 Otemae, Chuo-ku, Osaka, Osaka, 541-8567, Japan., Inoue S; Department of Cosmetic Health Science, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu, 501-1196, Japan. Electronic address: inoshin@gifu-pu.ac.jp.
Jazyk: angličtina
Zdroj: Archives of biochemistry and biophysics [Arch Biochem Biophys] 2024 Sep; Vol. 759, pp. 110098. Date of Electronic Publication: 2024 Jul 14.
DOI: 10.1016/j.abb.2024.110098
Abstrakt: Mouse transmembrane protein 2 (mTMEM2) has been identified as a hyaluronidase, which has extracellularly G8 and GG domains and PbH1 repeats; however, our previously study showed that human TMEM2 (hTMEM2) is not a catalytic hyaluronidase due to the absence of the critical amino acid residues (His248/Ala303) in the GG domain. Naked mole-rats (NMRs) accumulate abundant high-molecular weight hyaluronan (HA) in their tissues, suggesting decreased HA degradation. Therefore, we aimed to evaluate the HA-degrading activity of NMR TMEM2 (nmrTMEM2) and compare it with those of mTMEM2 and hTMEM2. The amino acid residues of nmrTMEM2 (Asn247/Val302) are similar to Asn248/Phe303 of hTMEM2, and nmrTMEM2-expressing HEK293T cells showed negligible activity. We confirmed the significance of these amino acid residues using an inactive chimeric TMEM2 with the human GG domain, which acquired catalytic activity when Asn248/Phe303 was substituted with His248/Ala303. Semi-quantitative comparison of the activities of the membrane-fractions derived from m/h/nmrTMEM2-expressing HEK293T cells revealed that at least 20- and 14-fold higher amounts of nmr/hTMEM2 were required to degrade HA to the same extent as by mTMEM2. Thus, unlike mTMEM2, nmrTMEM2 is not a physiological hyaluronidase. The inability of nmrTMEM2 to degrade HA might partially account for the high-molecular-weight HA accumulation in NMR tissues.
Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare.
(Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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