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Protein-coding gene in the species Homo sapiens
Major facilitator superfamily domain-containing protein 2 (MFSD2 or MFSD2A ) -- also known as sodium-dependent lysophosphatidylcholine symporter 1 -- is a protein that in humans is encoded by the MFSD2A gene .[ 5] membrane transport protein that is expressed in the endothelium of the blood–brain barrier (BBB) and has an essential role in BBB formation and function.[ 5] Genetic ablation of MFSD2A results in leaky BBB and increases central nervous system endothelial cell vesicular transcytosis without otherwise affecting tight junctions .[ 6] atypical SLC ,[ 7] SLC transporter.[ 8] phylogenetically to AMTF 8.[ 8]
In addition to transport of other lysophosphatidylcholines across the BBB, MSFD2A is the primary mechanism for docosahexaenoic acid (DHA, an omega-3 fatty acid ) uptake and transport into the brain.[ 5] tunicamycin .[ 9] [ 10] [ 11]
Complete loss of MFSD2A in human leads to a recessive lethal microcephaly syndrome consisting of enlarged lateral ventricles and underdevelopment of the cerebellum and brainstem. This is presumably due to loss of uptake of essential polyunsaturated fatty acids by the brain endothelial cells, which utilize MFSD2A as a transporter for these fats. Serum from patients showed elevated levels of essential polyunsaturated fatty acids, presumably due to the inability of vascular cells to uptake these lipids in the absence of protein function. Without the ability to uptake these fats into endothelial cells, there is breakdown of the blood-brain-barrier and loss of brain volume. This was demonstrated in a zebrafish model by intracardiac injection of dye, which was found to extravasate into the brain parenchyma following inactivating one of the paralogues of MSFD2A known as mfsd2aa.[ 12]
^ a b c GRCh38: Ensembl release 89: ENSG00000168389 – Ensembl , May 2017^ a b c GRCm38: Ensembl release 89: ENSMUSG00000028655 – Ensembl , May 2017^ "Human PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .^ "Mouse PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .^ a b c "Sodium-dependent lysophosphatidylcholine symporter 1" . UniProt . Retrieved 2 April 2016 .^ Ben-Zvi A, Lacoste B, Kur E, Andreone BJ, Mayshar Y, Yan H, Gu C (May 2014). "Mfsd2a is critical for the formation and function of the blood-brain barrier" . Nature . 509 (7501): 507–11. Bibcode :2014Natur.509..507B . doi :10.1038/nature13324 . PMC 4134871 PMID 24828040 . ^ Perland, Emelie; Fredriksson, Robert (March 2017). "Classification Systems of Secondary Active Transporters". Trends in Pharmacological Sciences . 38 (3): 305–315. doi :10.1016/j.tips.2016.11.008 . ISSN 1873-3735 . PMID 27939446 . ^ a b Perland, Emelie; Bagchi, Sonchita; Klaesson, Axel; Fredriksson, Robert (September 2017). "Characteristics of 29 novel atypical solute carriers of major facilitator superfamily type: evolutionary conservation, predicted structure and neuronal co-expression" . Open Biology . 7 (9): 170142. doi :10.1098/rsob.170142 . ISSN 2046-2441 . PMC 5627054 PMID 28878041 . ^ Angers M, Uldry M, Kong D, Gimble JM, Jetten AM (November 2008). "Mfsd2a encodes a novel major facilitator superfamily domain-containing protein highly induced in brown adipose tissue during fasting and adaptive thermogenesis" . Biochem J . 416 (3): 347–55. doi :10.1042/BJ20080165 . PMC 2587516 PMID 18694395 . ^ "Entrez Gene: MFSD2 major facilitator superfamily domain containing 2" .^ Reiling JH, Clish CB, Carette JE, Varadarajan M, Brummelkamp TR, Sabatini DM (July 2011). "A haploid genetic screen identifies the major facilitator domain containing 2A (MFSD2A) transporter as a key mediator in the response to tunicamycin" . Proc Natl Acad Sci U S A . 108 (29): 11756–65. Bibcode :2011PNAS..10811756R . doi :10.1073/pnas.1018098108 PMC 3141996 PMID 21677192 . ^ Nat Genet. 2015 Jul;47(7):809-13
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