FASTK 家族蛋白调节线粒体 RNA 的加工和稳定性
中文名称
通路描述
Fas-activated serine/threonine kinase (FASTK) 及其同源物 FASTKD1-5 均含有三个保守结构域（FAST_1、FAST_2 和 RAP），可结合 RNA（Castello et al. 2012, Baltz et al. 2012）。FASTKD1-5 和 FASTK 的短 isoform 定位于线粒体，参与调节 RNA 的加工和稳定性（Simarro et al. 2010, reviewed in Jourdain et al. 2017）。FASTK 与 MT-ND6 mRNA 的 3' 端结合，保护 mRNA 免受 degradosome 和 SUPV3L1:PNPT1 的降解（Jourdain et al. 2015）。MT-ND6 mRNA 是异常的，其加工来自大 L 链前体，未包含 flanking tRNA 基因，因此未经历 RNAse P 和 RNase Z 的常规加工。FASTK 可能参与未表征的非经典 RNA 加工机制，或保护此类机制产生的 3' 端。FASTKD1 通过未表征的机制减少 MT-ND3 mRNA 的丰度（Boehm et al. 2017）。FASTKD2 结合 16S rRNA 和 MT-ND6 mRNA，参与其加工和表达（Antonicka and Shoubridge 2015, Popow et al. 2015）。FASTKD2 与多个线粒体蛋白相互作用，包括 MTERFD1、TRUB2、WBSCR16 和 NGRN（Antonicka et al. 2017）。FASTKD3 增加五种线粒体 mRNA（MT-ND2、MT-ND3、MT-CYB、MT-CO2 和 MT-ATP8/6 双义序 mRNA）的水平，并通过未表征的机制增加 MT-CO1 mRNA 的翻译（Boehm et al. 2016, Ohkubo et al. 2021）。TBRG4（FASTKD4）结合从 H 链转录的大部分 RNA，增强 MT-ATP8/6、MT-CO1、MT-CO2、MT-CO3、MT-ND3、MT-CYB 和 MT-ND5 mRNA 的表达水平（Wolf and Mootha 2014, Boehm et al. 2017, Ohkubo et al. 2021）。TBRG4 稳定 MT-CO1、MT-ND3 和 MT-CO2 mRNA，并协助 MT-ND5 和 MT-CYB mRNA 的加工（Boehm et al. 2017, Ohkubo et al. 2021）。FASTKD5 结合 12S rRNA 和除 MT-ND3 外的所有 mRNA，减少 MT-ATP8/6、MT-CO1、MT-CO3、MT-ND5 和 MT-CYB mRNA 的水平（Antonicka and Shoubridge 2015, Ohkubo et al. 2021）。
英文描述
Mechanical load activates signaling by PIEZO1 and integrins in osteocytes Osteocytes are mechanosensory cells in mineralized bone that have dendrites extending through lacunae (parallel with collagen fibers) and canaliculi (perpendicular to collagen fibers) to make contact with other osteocytes and with osteoblasts on the bone surface (reviewed in Moriishi and Komori 2022). Fluid flow and pressure in the lacunae and canaliculi are sensed by the dendrites and communicated to the cell body (inferred from mouse osteocytes in Burra et al. 2010), resulting in secretion of anabolic factors such as prostaglandin E2 (PGE2) that act to strengthen the bone (Siller-Jackson et al. 2008, Riquelme et al. 2021, reviewed in Zhao et al. 2023).
Mechanosensitive PIEZO1 channels are opened by membrane stretch and transport calcium and sodium ions along their concentration gradients into the osteocyte. T-type voltage-sensitive calcium channels (CaV2 channles) open secondarily and augment the calcium influx. Cytosolic calcium activates Pannexin-1 (PANX1) channels, which transport ATP from the cytosol to the extracellular region. Extracellular ATP binds P2RX7 (P2X7) receptors located in a complex with PANX1. P2RX7 then transports cations including calcium into the cell and may act in an autocrine and paracrine manner to propagate waves of calcium influx.
Integrin alphaV:beta3 (ITGAV:ITGB3) located in the plasma membrane of dendrites binds the extracellular matrix of the lacunar or canicular wall. Fluid flow activates ITGAV:ITGB3 to phosphorylate AKT1 via a PI3K-dependent mechanism (Riquelme et al. 2021). Phospho-AKT1 then phosphorylates integrin alpha5 (ITGA5) and Connexin43 (GJA1) located in a complex in the plasma membrane of the cell body. Phospho-GJA1 transports ATP (Kang et al. 2008) and PGE2 from the cytosol to the extracellular region (reviewed in Zhao et al. 2023).
CaV3.2 voltage-sensitive calcium channels also directly interact with the extracellular proteoglycan perlecan (PLN, PLC, HSPG2) and the alpha2delta1 subunit of the CaV3.2 complex (Reyes Fernandez et al. 2022). Physical force on perlecan may thus affect calcium transport by the CaV3.2 channels.
Mechanosensitive PIEZO1 channels are opened by membrane stretch and transport calcium and sodium ions along their concentration gradients into the osteocyte. T-type voltage-sensitive calcium channels (CaV2 channles) open secondarily and augment the calcium influx. Cytosolic calcium activates Pannexin-1 (PANX1) channels, which transport ATP from the cytosol to the extracellular region. Extracellular ATP binds P2RX7 (P2X7) receptors located in a complex with PANX1. P2RX7 then transports cations including calcium into the cell and may act in an autocrine and paracrine manner to propagate waves of calcium influx.
Integrin alphaV:beta3 (ITGAV:ITGB3) located in the plasma membrane of dendrites binds the extracellular matrix of the lacunar or canicular wall. Fluid flow activates ITGAV:ITGB3 to phosphorylate AKT1 via a PI3K-dependent mechanism (Riquelme et al. 2021). Phospho-AKT1 then phosphorylates integrin alpha5 (ITGA5) and Connexin43 (GJA1) located in a complex in the plasma membrane of the cell body. Phospho-GJA1 transports ATP (Kang et al. 2008) and PGE2 from the cytosol to the extracellular region (reviewed in Zhao et al. 2023).
CaV3.2 voltage-sensitive calcium channels also directly interact with the extracellular proteoglycan perlecan (PLN, PLC, HSPG2) and the alpha2delta1 subunit of the CaV3.2 complex (Reyes Fernandez et al. 2022). Physical force on perlecan may thus affect calcium transport by the CaV3.2 channels.
所含基因
16 个基因