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  1. 教員研究業績
  2. 薬物治療学研究室
  3. 原著論文

Role of phosphate transporter PiT-2 in the pathogenesis of primary brain calcification

https://gifu-pu.repo.nii.ac.jp/records/14761
https://gifu-pu.repo.nii.ac.jp/records/14761
1af2f16f-3d8b-416c-a375-218c9dba33d0
Item type 研究室原著論文(1)
公開日 2023-03-13
タイトル
タイトル Role of phosphate transporter PiT-2 in the pathogenesis of primary brain calcification
タイトル
タイトル Role of phosphate transporter PiT-2 in the pathogenesis of primary brain calcification
言語 en
言語
言語 eng
資源タイプ
資源タイプ識別子 http://purl.org/coar/resource_type/c_6501
資源タイプ journal article
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アクセス権 metadata only access
アクセス権URI http://purl.org/coar/access_right/c_14cb
抄録
値 Primary brain calcification (PBC), also known as idiopathic basal ganglia calcification (IBGC), primary familial brain calcification (PFBC) and so on, is a rare intractable disease characterized by abnormal mineral deposits, including mostly calcium in the basal ganglia, thalamus, and cerebellum. The causative gene of familial PBC is SLC20A2, which encodes the phosphate transporter PiT-2. Despite this knowledge, the molecular mechanism underlying SLC20A2-associated PBC remains unclear. In the present study, we investigated whether haploinsufficiency or a dominant-negative mechanism reduced Pi uptake in two PiT-2 variants (T115 M and R467X). We demonstrated that the presence of T115 M or R467X had no dominant-negative effect on Pi transport activity of wild-type (WT). In addition, the subcellular localization of R467X completely differed from that of WT, indicating that there is no interaction between R467X and WT. Conversely, T115 M and WT showed almost the same localization. Therefore, we examined the interaction between T115 M and WT using the bioluminescence resonance energy transfer (BRET) method. Although WT and T115 M interact with each other, T115 M does not inhibit WT's Pi transport activity. These results suggest that the role of SLC20A2 in the pathogenesis of PBC may involve decreased intracellular Pi uptake by a haploinsufficiency mechanism rather than a dominant-negative mechanism; agents promoting PiT-2 dimerization may be promising potential therapeutic agents for PBC.
書誌情報 Biochemical and Biophysical Research Communications
en : Biochemical and Biophysical Research Communications

巻 640, p. 21-25, 発行日 2023-01-15
DOI
値 10.1016/j.bbrc.2022.11.106
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