Current Structural Knowledge on the CNNM Family of Magnesium Transport Mediators

• Published in: International journal of molecular sciences Vol. 20; no. 5; p. 1135
• Main Authors: Giménez-Mascarell, Paula, González-Recio, Irene, Fernández-Rodríguez, Cármen, Oyenarte, Iker, Müller, Dominik, Martínez-Chantar, María Luz, Martínez-Cruz, Luis Alfonso
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 06.03.2019; MDPI
• Subjects: Amino acids; Blood pressure; Cell division; Diabetes; Magnesium; Membranes; Mutation; Peptides; Proteins; Review; Small intestine; Sperm; ACDP; CNNM; magnesium homeostasis; cNMP domain; Jalili syndrome; hypomagnesemia; magnesium transport; CBS domain; cancer; CNBH domain
• ISSN: 1422-0067; 1661-6596; 1422-0067
• 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 Mg2+/Co2+ efflux protein CorC and the Mg2+ channel MgtE.