Current Structural Knowledge on the CNNM Family of Magnesium Transport Mediators
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 Hypomagnesem...
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| Published in | International journal of molecular sciences Vol. 20; no. 5; p. 1135 |
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| Main Authors | , , , , , , |
| Format | Journal Article |
| Language | English |
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06.03.2019
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| ISSN | 1422-0067 1661-6596 1422-0067 |
| DOI | 10.3390/ijms20051135 |
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| Abstract | 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. |
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| AbstractList | 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.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. 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. Mg also plays a key role in the stabilization of cell membranes, neuronal transmission [2], cardiac excitability, regulation of blood pressure, maintenance of nerve and muscle functions, and in the regulation of the glucose and insulin metabolism [3,4]. Among the Mg2+-wasting-related disorders are osteoporosis, abnormal brain development, neurological alterations, immunodeficiency, impaired motility of sperm, diabetes, hypertension, cancer, and several rare diseases such as familial hypomagnesemia or Jalili Syndrome [6,9,12,13,14,15,16,17,18,19]. CNNM1 appears to act as a cytosolic copper chaperone [28] and is mainly found in the testis and brain [11,20,22,29,30], whereas low expression levels are found in the stomach, kidney, skeletal muscles, heart, lungs, liver, small intestine, colon, and spleen [29]. The N-terminal region is extracellular and shares the lowest amino acid sequence similarity (~19%) among the four members encoded in the human genome. 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. 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 2+ /Co 2+ efflux protein CorC and the Mg 2+ channel MgtE. |
| Author | Martínez-Cruz, Luis Alfonso Martínez-Chantar, María Luz Oyenarte, Iker Giménez-Mascarell, Paula González-Recio, Irene Müller, Dominik Fernández-Rodríguez, Cármen |
| AuthorAffiliation | 3 Liver Disease Lab, CIC bioGUNE, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 48160 Derio, Bizkaia, Spain 1 Center for Cooperative Research in Biosciences (CIC bioGUNE), Bizkaia Science and Technology Park Bld 800, 48160 Derio, Bizkaia, Spain; pgimenez@cicbiogune.es (P.G.-M.); irecio@cicbiogune.es (I.G.-R.); cfernandez@cicbiogune.es (C.F.-R.); ioyenarte@cicbiogune.es (I.O.); mlmartinez@cicbiogune.es (M.L.M.-C.) 2 Department of Pediatric Gastroenterology, Nephrology and Metabolic Disorders, Charité Universitäts Medizin, Berlin, 13353 Berlin, Germany; Dominik.Mueller@charite.de |
| AuthorAffiliation_xml | – name: 3 Liver Disease Lab, CIC bioGUNE, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 48160 Derio, Bizkaia, Spain – name: 2 Department of Pediatric Gastroenterology, Nephrology and Metabolic Disorders, Charité Universitäts Medizin, Berlin, 13353 Berlin, Germany; Dominik.Mueller@charite.de – name: 1 Center for Cooperative Research in Biosciences (CIC bioGUNE), Bizkaia Science and Technology Park Bld 800, 48160 Derio, Bizkaia, Spain; pgimenez@cicbiogune.es (P.G.-M.); irecio@cicbiogune.es (I.G.-R.); cfernandez@cicbiogune.es (C.F.-R.); ioyenarte@cicbiogune.es (I.O.); mlmartinez@cicbiogune.es (M.L.M.-C.) |
| Author_xml | – sequence: 1 givenname: Paula surname: Giménez-Mascarell fullname: Giménez-Mascarell, Paula – sequence: 2 givenname: Irene surname: González-Recio fullname: González-Recio, Irene – sequence: 3 givenname: Cármen surname: Fernández-Rodríguez fullname: Fernández-Rodríguez, Cármen – sequence: 4 givenname: Iker surname: Oyenarte fullname: Oyenarte, Iker – sequence: 5 givenname: Dominik orcidid: 0000-0002-3478-1576 surname: Müller fullname: Müller, Dominik – sequence: 6 givenname: María Luz surname: Martínez-Chantar fullname: Martínez-Chantar, María Luz – sequence: 7 givenname: Luis Alfonso orcidid: 0000-0002-5856-9377 surname: Martínez-Cruz fullname: Martínez-Cruz, Luis Alfonso |
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| Keywords | ACDP CNNM magnesium homeostasis cNMP domain Jalili syndrome hypomagnesemia magnesium transport CBS domain cancer CNBH domain |
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| SubjectTerms | Amino acids Blood pressure Cell division Diabetes Magnesium Membranes Mutation Peptides Proteins Review Small intestine Sperm |
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| Title | Current Structural Knowledge on the CNNM Family of Magnesium Transport Mediators |
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