SLC15A4:TASL-dependent IRF5 激活
中文名称
通路描述
该 Reactome 模块描述了通过 SLC15A4:TASL 轴介导的 Toll 样受体 7 (TLR7)、TLR8 或 TLR9 诱导的干扰素调节因子 5 (IRF5) 激活。溶质载体家族 15 成员 4 (SLC15A4，也称为 PHT1) 是一种质子耦合的 L-组氨酸/寡肽转运蛋白。除了其转运功能外，SLC15A4 还调节晚期内体/溶酶体中的 TLR7-9 信号通路。SLC15A4 作为信号支架，招募与 SLC15A4 结合的蛋白 TASL 到溶酶体的胞质表面 (Heinz LX. et al., 2020; Custodio TF et al., 2023; Chen X et al., 2023)。当内体 TLR 信号被激活时，TASL 发生磷酸化并招募 IRF5 到其 pLxIS 基序上 (Heinz LX. et al., 2020)。SLC15A4:TASL 复合物通过 IKBKB (IKKβ) 促进 IRF5 磷酸化，并在 TLR7-TLR9 下游导致 IRF5 同源二聚化 (Heinz LX. et al., 2020; Zhang H et al., 2023; Chen X et al., 2023; Boeszoermeny A et al., 2023)。一旦激活，IRF5 转运至细胞核，诱导编码 I 型干扰素和促炎细胞因子的基因转录。SLC15A4:TASL:IRF5 通路的过度激活，通常由内源性核酸的检测引起，导致 I 型干扰素产生增加，并与系统性红斑狼疮 (SLE) 等炎症疾病的发病机制相关 (Odhams CA et al., 2019; Heinz LX. et al., 2020; Kobayashi T et al., 2021)。
英文描述
Acetylcholine inhibits contraction of outer hair cells Outer hair cells (OHCs) are synapsed with efferent cholinergic medial olivocochlear fibers (reviewed in Fritzsch and Elliott 2017, Fuchs and Lauer 2019). Acetylcholine released at the synapse binds an unusual, nicotine-antagonized, nicotinic receptor comprising CHRNA9 and CHRNA10. Upon binding acetylcholine, CHRNA9:CHRNA10 transports calcium ions into the OHC. The calcium activates nearby SK2 potassium channels (KCNN2, small potassium current channels) and BK potassium channels (KCNMA1:KCNMB1, big potassium current channels) which extrude potassium ions, hyperpolarize the OHC, and inhibit activation of the OHC.
The overall effects of acetylcholine on OHCs are complex. OHCs exhibit fast motility caused by voltage effect on SLC26A5 and slow motility caused by cytoskeleton organization.
The overall effects of acetylcholine on OHCs are complex. OHCs exhibit fast motility caused by voltage effect on SLC26A5 and slow motility caused by cytoskeleton organization.
所含基因
5 个基因