Basolateral Mg Extrusion via CNNM4 Mediates Transcellular Mg Transport across Epithelia: A Mouse Model

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Transcellular Mg²⁺ transport across epithelia, involving both apical entry and basolateral extrusion, is essential for magnesium homeostasis, but molecules involved in basolateral extrusion have not yet been identified. Here, we show that CNNM4 is the basolaterally located Mg²⁺ extrusion molecule. CNNM4 is strongly expressed in intestinal epithelia and localizes to their basolateral membrane. CNNM4-knockout mice showed hypomagnesemia due to the intestinal malabsorption of magnesium, suggesting its role in Mg²⁺ extrusion to the inner parts of body. Imaging analyses revealed that CNNM4 can extrude Mg²⁺ by exchanging intracellular Mg²⁺ with extracellular Na⁺. Furthermore, CNNM4 mutations cause Jalili syndrome, characterized by recessive amelogenesis imperfecta with cone-rod dystrophy. CNNM4-knockout mice showed defective amelogenesis, and CNNM4 again localizes to the basolateral membrane of ameloblasts, the enamel-forming epithelial cells. Missense point mutations associated with the disease abolish the Mg²⁺ extrusion activity. These results demonstrate the crucial importance of Mg²⁺ extrusion by CNNM4 in organismal and topical regulation of magnesium.

Vyšlo v časopise: Basolateral Mg Extrusion via CNNM4 Mediates Transcellular Mg Transport across Epithelia: A Mouse Model. PLoS Genet 9(12): e32767. doi:10.1371/journal.pgen.1003983
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1003983

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