Center for Cooperative Research in Biosciences (CIC bioGUNE), Bizkaia Science and Technology Park Bld 800, 48160 Derio, Bizkaia, Spain.
Department of Pediatric Gastroenterology, Nephrology and Metabolic Disorders, Charité Universitäts Medizin, Berlin, 13353 Berlin, Germany.
Int J Mol Sci. 2019 Mar 6;20(5):1135. doi: 10.3390/ijms20051135.
The cyclin and cystathionine β-synthase (CBS) domain magnesium transport mediators, CNNMs, are key players in maintaining the homeostasis of magnesium in different organs. The human family includes four members, whose impaired activity causes diseases such as Jalili Syndrome or Familial Hypomagnesemia, but is also linked to neuropathologic disorders, altered blood pressure, and infertility. Recent findings demonstrated that CNNMs are associated with the highly oncogenic phosphatases of the regenerating liver to promote tumor growth and metastasis, which has attracted renewed focus on their potential exploitation as targets for cancer treatment. However, the exact function of CNNMs remains unclear and is subject to debate, proposed as either direct transporters, sensors, or homeostatic factors. This review gathers the current structural knowledge on the CNNM family, highlighting similarities and differences with the closely related structural partners such as the bacterial Mg/Co efflux protein CorC and the Mg channel MgtE.
细胞周期蛋白和半胱氨酸 β-合酶 (CBS) 域镁转运介质 (CNNMs) 是维持不同器官镁内稳态的关键因素。人类家族包括四个成员，其活性受损会导致 Jalili 综合征或家族性低镁血症等疾病，但也与神经病理紊乱、血压改变和不孕有关。最近的研究结果表明，CNNMs 与再生肝脏中的高度致癌磷酸酶有关，可促进肿瘤生长和转移，这引起了人们对其作为癌症治疗靶点的潜在利用的重新关注。然而，CNNMs 的确切功能仍不清楚，存在争议，被认为是直接转运体、传感器或内稳态因子。本综述收集了目前关于 CNNM 家族的结构知识，强调了与密切相关的结构伴侣（如细菌 Mg/Co 外排蛋白 CorC 和 Mg 通道 MgtE）的相似性和差异。
