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IMPdh2 在星形胶质细胞干细胞突起的分支位点和末端形成斑点。

IMPDH2 forms spots at branching sites and distal ends of astrocyte stem processes.

机构信息

Department of Psychiatry and Behavioral Sciences, Tokyo Medical and Dental University Graduate School, Tokyo, Japan.

Department of Neuropathology, Medical Research Institute and Center for Brain Integration Research, Tokyo Medical and Dental University, Tokyo, Japan.

出版信息

Genes Cells. 2024 Feb;29(2):150-158. doi: 10.1111/gtc.13088. Epub 2023 Nov 27.

Abstract

Inosine monophosphate dehydrogenase (IMPDH) is a rate-limiting enzyme in the de novo GTP biosynthesis pathway. Recent studies suggest that IMPDH2, an isoform of IMPDH, can localize to specific subcellular compartments under certain conditions and regulate site-specific GTP availability and small GTPase activity in invasive cancer cells. However, it is unclear whether IMPDH2 plays a site-specific regulatory role in subcellular functions in healthy cells. In this study, we focused on brain cells and examined the localization pattern of IMPDH2. We discovered that IMPDH2 forms localized spots in the astrocytes of the adult mouse hippocampus. Further analysis of spot distribution in primary astrocyte cultures revealed that IMPDH2 spots are predominantly localized on branching sites and distal ends of astrocyte stem processes. Our findings suggest a potential unidentified role for IMPDH2 and GTP synthesis specifically at specialized nodes of astrocyte branches.

摘要

肌苷单磷酸脱氢酶(IMPDH)是从头合成 GTP 途径中的限速酶。最近的研究表明,IMPDH 的一种同工酶 IMPDH2 在某些条件下可以定位于特定的亚细胞隔室,并调节侵袭性癌细胞中特定部位的 GTP 可用性和小 GTP 酶活性。然而,目前尚不清楚 IMPDH2 是否在健康细胞的亚细胞功能中发挥特定部位的调节作用。在这项研究中,我们专注于脑细胞,并研究了 IMPDH2 的定位模式。我们发现 IMPDH2 在成年小鼠海马体的星形胶质细胞中形成局部斑点。对原代星形胶质细胞培养物中斑点分布的进一步分析表明,IMPDH2 斑点主要定位于星形胶质细胞干突起的分支位点和远端。我们的研究结果表明,IMPDH2 和 GTP 合成在星形胶质细胞分支的专门节点处具有潜在的未知作用。

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