The proton-coupled folate transporter (PCFT-SLC46A1) and the syndrome of systemic and cerebral folate deficiency of infancy: Hereditary folate malabsorption

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• 作者：Rongbao Zhao^a ; ^b ; Srinivas Aluri^a ; ^b ; I. David Goldman^a ; ^b ; ^{i.david.goldman@einstein.yu.edu}
• 关键词：Proton-coupled folate transporter ; PCFT ; SLC46A1 ; Reduced folate carrier ; RFC ; SLC19A1 ; Folate receptors ; FRα ; Folates ; Folic acid ; Methotrexate ; Pemetrexed ; Hereditary folate malabsorption ; HFM ; Cerebral folate deficiency ; CFD
• 刊名：Molecular Aspects of Medicine
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：53
• 期：Complete
• 页码：57-72
• 全文大小：1110 K
• 卷排序：53

文摘

The proton-coupled folate transporter (PCFT-SLC46A1) is the mechanism by which folates are absorbed across the brush-border membrane of the small intestine. The transporter is also expressed in the choroid plexus and is required for transport of folates into the cerebrospinal fluid. Loss of PCFT function, as occurs in the autosomal recessive disorder “hereditary folate malabsorption” (HFM), results in a syndrome characterized by severe systemic and cerebral folate deficiency. Folate-receptor alpha (FRα) is expressed in the choroid plexus, and loss of function of this protein, as also occurs in an autosomal recessive disorder, results solely in “cerebral folate deficiency” (CFD), the designation for this disorder. This paper reviews the current understanding of the functional and structural properties and regulation of PCFT, an electrogenic proton symporter, and contrasts PCFT properties with those of the reduced folate carrier (RFC), an organic anion antiporter, that is the major route of folate transport to systemic tissues. The clinical characteristics of HFM and its treatment, based upon the thirty-seven known cases with the clinical syndrome, of which thirty have been verified by genotype, are presented. The ways in which PCFT and FRα might interact at the level of the choroid plexus such that each is required for folate transport from blood to cerebrospinal fluid are considered along with the different clinical presentations of HFM and CFD.