TRPM7 激酶通过调节异三聚体 G 蛋白限制受体诱导的钙释放。
The TRPM7 kinase limits receptor-induced calcium release by regulating heterotrimeric G-proteins.
机构信息
Center for Biomedical Research, The Queen's Medical Center, 1301 Punchbowl St., Honolulu, HI, 96813, USA.
John A. Burns School of Medicine, University of Hawaii Cancer Center, University of Hawaii, 651 Ilalo St, Honolulu, HI, 96813, USA.
出版信息
Cell Mol Life Sci. 2018 Aug;75(16):3069-3078. doi: 10.1007/s00018-018-2786-z. Epub 2018 Mar 2.
The melastatin-related transient receptor potential member 7 (TRPM7) is a unique fusion protein with both ion channel function and enzymatic α-kinase activity. TRPM7 is essential for cellular systemic magnesium homeostasis and early embryogenesis; it promotes calcium transport during global brain ischemia and emerges as a key player in cancer growth. TRPM7 channels are negatively regulated through G-protein-coupled receptor-stimulation, either by reducing cellular cyclic adenosine monophosphate (cAMP) or depleting phosphatidylinositol bisphosphate (PIP) levels in the plasma membrane. We here identify that heterologous overexpression of human TRPM7-K1648R mutant will lead to disruption of protease or purinergic receptor-induced calcium release. The disruption occurs at the level of G, which requires intact TRPM7 kinase phosphorylation activity for orderly downstream signal transduction to activate phospholipase (PLC)β and cause calcium release. We propose that this mechanism may support limiting GPCR-mediated calcium signaling in times of insufficient cellular ATP supply.
金属硫蛋白相关瞬时受体电位通道 7 型（TRPM7）是一种独特的融合蛋白，具有离子通道功能和酶 α-激酶活性。TRPM7 对细胞内镁稳态和早期胚胎发生至关重要；它促进全脑缺血期间的钙转运，并成为癌症生长的关键因素。TRPM7 通道通过 G 蛋白偶联受体刺激负调控，要么通过降低细胞环腺苷酸单磷酸（cAMP）水平，要么耗尽质膜中双磷酸肌醇（PIP）水平。我们在这里发现，人源 TRPM7-K1648R 突变体的异源过表达将导致蛋白酶或嘌呤能受体诱导的钙释放中断。这种中断发生在 G 水平，需要完整的 TRPM7 激酶磷酸化活性来有序地向下游信号转导，以激活磷脂酶（PLC）β并引起钙释放。我们提出，这种机制可能支持在细胞 ATP 供应不足时限制 GPCR 介导的钙信号。
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