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Basolateral Mg2+ Extrusion via CNNM4 Mediates Transcellular Mg2+ Transport across Epithelia: A Mouse Model
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نویسنده
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yamazaki d. ,funato y. ,miura j. ,sato s. ,toyosawa s. ,furutani k. ,kurachi y. ,omori y. ,furukawa t. ,tsuda t. ,kuwabata s. ,mizukami s. ,kikuchi k. ,miki h.
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منبع
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plos genetics - 2013 - دوره : 9 - شماره : 12
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چکیده
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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. © 2013 yamazaki et al.
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آدرس
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department of cellular regulation,research institute for microbial diseases,osaka university,suita, Japan, department of cellular regulation,research institute for microbial diseases,osaka university,suita, Japan, division for interdisciplinary dentistry,dental hospital,osaka university,suita, Japan, department of oral pathology,graduate school of dentistry,osaka university,suita, Japan, department of oral pathology,graduate school of dentistry,osaka university,suita, Japan, department of pharmacology,graduate school of medicine,osaka university,suita, Japan, department of pharmacology,graduate school of medicine,osaka university,suita, Japan, laboratory for molecular and developmental biology,institute for protein research,osaka university,suita,japan,presto,japan science and technology corporation,kawaguchi, Japan, laboratory for molecular and developmental biology,institute for protein research,osaka university,suita,japan,crest,japan science and technology corporation,kawaguchi, Japan, department of applied chemistry,graduate school of engineering,osaka university,suita, Japan, department of applied chemistry,graduate school of engineering,osaka university,suita, Japan, division of advanced science and biotechnology,graduate school of engineering,osaka university,suita, Japan, division of advanced science and biotechnology,graduate school of engineering,osaka university,suita, Japan, department of cellular regulation,research institute for microbial diseases,osaka university,suita, Japan
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Authors
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