人源磷脂 scramblases 在细胞凋亡中的作用：概述。

The role of human phospholipid scramblases in apoptosis: An overview.

机构信息

Applied and Industrial Microbiology Laboratory, Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, Indian Institute of Technology Madras, Chennai 600 036, India.

出版信息

Biochim Biophys Acta Mol Cell Res. 2017 Dec;1864(12):2261-2271. doi: 10.1016/j.bbamcr.2017.08.008. Epub 2017 Aug 24.

DOI:10.1016/j.bbamcr.2017.08.008

PMID:28844836

Abstract

Human phospholipid scramblases (hPLSCRs) are a family of four homologous single pass transmembrane proteins (hPLSCR1-4) initially identified as the proteins responsible for Ca mediated bidirectional phospholipid translocation in plasma membrane. Though in-vitro assays had provided evidence, the role of hPLSCRs in phospholipid translocation is still debated. Recent reports revealed a new class of proteins, TMEM16 and Xkr8 to exhibit scramblase activity challenging the function of hPLSCRs. Apart from phospholipid scrambling, numerous reports have emphasized the multifunctional roles of hPLSCRs in key cellular processes including tumorigenesis, antiviral defense, protein and DNA interactions, transcriptional regulation and apoptosis. In this review, the role of hPLSCRs in mediating cell death through phosphatidylserine exposure, interaction with death receptors, cardiolipin exposure, heavy metal and radiation induced apoptosis and pathological apoptosis followed by their involvement in cancer cells are discussed. This review aims to connect the multifunctional characteristics of hPLSCRs to their decisive involvement in apoptotic pathways.

摘要

人源磷脂翻转酶（hPLSCRs）是一个家族的四个同源单次跨膜蛋白（hPLSCR1-4），最初被确定为负责 Ca 介导的质膜中双向磷脂易位的蛋白。尽管体外实验提供了证据，但 hPLSCRs 在磷脂易位中的作用仍存在争议。最近的报道揭示了一类新的蛋白质，TMEM16 和 Xkr8，具有翻转酶活性，这对 hPLSCRs 的功能提出了挑战。除了磷脂翻转，许多报道强调了 hPLSCRs 在包括肿瘤发生、抗病毒防御、蛋白质和 DNA 相互作用、转录调节和细胞凋亡在内的关键细胞过程中的多功能作用。在这篇综述中，讨论了 hPLSCRs 通过暴露磷脂酰丝氨酸、与死亡受体相互作用、暴露心磷脂、重金属和辐射诱导的细胞凋亡以及随后的病理性细胞凋亡来介导细胞死亡的作用，以及它们在癌细胞中的参与。这篇综述旨在将 hPLSCRs 的多功能特性与其在细胞凋亡途径中的决定性参与联系起来。